Clinical Trials

Endovascular Repair of Abdominal Aortic AneurysmsNot Recruiting

The purpose of this study is to determine if it is safe and effective to use the TALENT AAA
Stent Graft System as a treatment for AAAs in patients who are also candidates for
conventional surgical aneurysm repair.

Stanford is currently not accepting patients for this trial.For more information, please contact Christopher Zarins, (650) 725 - 5227.

Abstract

Coronary computed tomography angiography (CCTA) allows for non-invasive assessment of obstructive coronary artery disease (CAD) beyond measures of stenosis severity alone. This assessment includes atherosclerotic plaque characteristics (APCs) and calculation of fractional flow reserve (FFR) from CCTA (FFRCT). Similarly, stress imaging by myocardial perfusion scintigraphy (MPS) provides vital information. To date, the diagnostic performance of integrated CCTA assessment versus integrated MPS assessment for diagnosis of vessel-specific ischemia remains underexplored.CREDENCE will enroll adult individuals with symptoms suspicious of CAD referred for non-emergent invasive coronary angiography (ICA), but without known CAD. All participants will undergo CCTA, MPS, ICA and FFR. FFR will be performed for lesions identified at the time of ICA to be ≥40 and <90 % stenosis, or those clinically indicated for evaluation. Study analyses will focus on diagnostic performance of CCTA versus MPS against invasive FFR reference standard. An integrated stenosis-APC-FFRCT metric by CCTA for vessel-specific ischemia will be developed from derivation cohort and tested against a validation cohort. Similarly, integrated metric by MPS for vessel-specific ischemia will be developed, validated and compared. An FFR value of ≤0.80 will be considered as ischemia causing. The primary endpoint will be the diagnostic accuracy of vessel territory-specific ischemia of integrated stenosis-APC-FFRCT measure by CCTA, compared with perfusion or perfusion-myocardial blood flow stress imaging testing, against invasive FFR.CREDENCE will determine the performance of integrated CCTA metric compared to integrated MPS measure for diagnosis of vessel-specific ischemia. If proven successful, this study may reduce the number of missed diagnoses and help to optimally predict ischemia-causing lesions.ClinicalTrials.gov, NCT02173275 . Registered on June 23, 2014.

Abstract

This study sought to determine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) for the diagnosis of lesion-specific ischemia in nonculprit vessels of patients with recent in ST-segment elevation myocardial infarction (STEMI).In patients with stable angina, FFRCT has high diagnostic performance in identification of ischemia-causing lesions. The potential value of FFRCT for assessment of multivessel disease in patients with recent STEMI has not been evaluated.Coronary CTA with calculation of FFRCT and invasive coronary angiography with FFR were performed 1 month after STEMI in patients with multivessel disease. Coronary CTA and invasive coronary angiography stenosis >50% were considered obstructive. Lesion-specific ischemia was assumed if FFRCT was ≤0.80. FFR ≤0.80 was the reference standard. To evaluate the influence of vessel size, the total coronary vessel lumen volume relative to left ventricular mass (volume-to-mass ratio) was calculated and compared with that of patients with stable angina.The study evaluated 124 nonculprit vessels from 60 patients. Accuracy, sensitivity, and specificity of FFRCT were 72%, 83%, and 66% versus 64% (p = 0.033), 93% (p = 0.15), and 49% (p < 0.001) for CTA and 72% (p = 1.00), 76% (p = 0.46), and 70% (p = 0.54) for invasive coronary angiography. Following STEMI, median volume-to-mass ratio was lower than in patients with stable angina, 53 versus 65 mm(3)/g (p = 0.009). In patients with volume-to-mass ratio ≥65 mm(3)/g (upper tertile) accuracy, sensitivity, and specificity of FFRCT were all 83% versus 56% (p = 0.009), 75% (p = 0.61), and 44% (p = 0.003) in patients with <49 mm(3)/g (lower tertile).The diagnostic performance of FFRCT for staged detection of ischemia in STEMI patients with multivessel disease is moderate. STEMI patients have a smaller vessel volume than do patients with stable angina. The diagnostic performance of FFRCT is influenced by the volume-to-mass ratio. This study does not support routine use of FFRCT in the post-STEMI setting. (Assessment of Coronary Stenoses Using Coronary CT-Angiography and Noninvasive Fractional Flow Reserve; NCT01739075).

Abstract

This study evaluated changes in aortic neck diameter after endovascular aneurysm repair (EVAR) using a balloon-expandable stent (BES) endograft compared with a commercially available self-expanding stent (SES) endograft. We hypothesized that forces applied to the aortic neck by SES endografts may induce aortic neck enlargement over time and that such enlargement may not occur in aneurysm patients treated with a device that does not use a proximal SES.This was a retrospective quantitative computed tomography (CT) image analysis of patients treated with the Nellix (Endologix, Irvine, Calif) BES (n = 49) or the Endurant II (Medtronic, Minneapolis, Minn) SES (n = 56) endograft from 2008 to 2010. Patients with preimplant, postimplant, and at least 1-year serial CT scans underwent quantitative morphometric assessment by two independent vascular radiologists blinded to the outcome results. Changes in the infrarenal neck over time were compared with the suprarenal aorta for each patient.Follow-up extended to 4.8 years for the BES and to 4.6 years for the SES, with no significant difference in median follow-up time (34 months for BESs and 24 months for SESs; P = .06). There were no differences in preimplant neck diameter (25.2 ± 0.9 mm vs 25.7 ± 1.1 mm; P = .54) or length (27.7 ± 3.7 mm vs 23.6 ± 3.7 mm; P = .12) between BESs and SESs at baseline. After implantation, neck diameter increased by 1.1 ± 0.5 mm in BES patients and 2.6 ± 0.5 mm in SES patients (P = .07) compared with the preoperative diameter. At 3 years, neck diameter increased by 0.5 ± 0.9 mm in BES patients and by 3.8 ± 1.0 mm in SES patients (P = .0002) compared with the first postoperative CT scan. The annual postimplant rate of increase in the infrarenal neck diameter was fivefold greater in SES patients (1.1 ± 0.1 mm/y) than in BES patients (0.22 ± 0.04 mm/y; P < .0001). There were no significant differences in the diameter of the suprarenal aorta at baseline or at 3 years and no differences in the annual rate of change in suprarenal aortic diameter between BES and SES endografts.EVAR using SES endografts resulted in progressive infrarenal aortic neck enlargement, whereas EVAR using BES endografts resulted in no neck enlargement over time. These data suggest that infrarenal neck enlargement after EVAR with SES endografts is likely related to the force exerted by SES elements rather than disease progression in the infrarenal neck.

Abstract

Percutaneous coronary intervention (PCI) based on fractional flow reserve (FFRcath) measurement during invasive coronary angiography (CAG) results in improved patient outcome and reduced healthcare costs. FFR can now be computed non-invasively from standard coronary CT angiography (cCTA) scans (FFRCT). The purpose of this study is to determine the potential impact of non-invasive FFRCT on costs and clinical outcomes of patients with suspected coronary artery disease in Japan. Clinical data from 254 patients in the HeartFlowNXT trial, costs of goods and services in Japan, and clinical outcome data from the literature were used to estimate the costs and outcomes of 4 clinical pathways: (1) CAG-visual guided PCI, (2) CAG-FFRcath guided PCI, (3) cCTA followed by CAG-visual guided PCI, (4) cCTA-FFRCT guided PCI. The CAG-visual strategy demonstrated the highest projected cost ($10,360) and highest projected 1-year death/myocardial infarction rate (2.4 %). An assumed price for FFRCT of US $2,000 produced equivalent clinical outcomes (death/MI rate: 1.9 %) and healthcare costs ($7,222) for the cCTA-FFRCT strategy and the CAG-FFRcath guided PCI strategy. Use of the cCTA-FFRCT strategy to select patients for PCI would result in 32 % lower costs and 19 % fewer cardiac events at 1 year compared to the most commonly used CAG-visual strategy. Use of cCTA-FFRCT to select patients for CAG and PCI may reduce costs and improve clinical outcome in patients with suspected coronary artery disease in Japan.

Abstract

It is likely that arrhythmias should be avoided for therapies based on human pluripotent stem cell (hPSC)-derived cardiomyocytes (CM) to be effective. Towards achieving this goal, we introduced light-activated channelrhodopsin-2 (ChR2), a cation channel activated with 480 nm light, into human embryonic stem cells (hESC). By using in vitro approaches, hESC-CM are able to be activated with light. ChR2 is stably transduced into undifferentiated hESC via a lentiviral vector. Via directed differentiation, hESC(ChR2)-CM are produced and subjected to optical stimulation. hESC(ChR2)-CM respond to traditional electrical stimulation and produce similar contractility features as their wild-type counterparts but only hESC(ChR2)-CM can be activated by optical stimulation. Here it is shown that a light sensitive protein can enable in vitro optical control of hESC-CM and that this activation occurs optimally above specific light stimulation intensity and pulse width thresholds. For future therapy, in vivo optical stimulation along with optical inhibition could allow for acute synchronization of implanted hPSC-CM with patient cardiac rhythms.

Abstract

Geometric factors including the size, shape, density, and spacing of pluripotent stem cell colonies play a significant role in the maintenance of pluripotency and in cell fate determination. These factors are impossible to control using standard tissue culture methods. As such, there can be substantial batch-to-batch variability in cell line maintenance and differentiation yield. Here, we demonstrate a simple, robust technique for pluripotent stem cell expansion and cardiomyocyte differentiation by patterning cell colonies with a silicone stencil. We have observed that patterning human induced pluripotent stem cell (hiPSC) colonies improves the uniformity and repeatability of their size, density, and shape. Uniformity of colony geometry leads to improved homogeneity in the expression of pluripotency markers SSEA4 and Nanog as compared with conventional clump passaging. Patterned cell colonies are capable of undergoing directed differentiation into spontaneously beating cardiomyocyte clusters with improved yield and repeatability over unpatterned cultures seeded either as cell clumps or uniform single cell suspensions. Circular patterns result in a highly repeatable 3D ring-shaped band of cardiomyocytes which electrically couple and lead to propagating contraction waves around the ring. Because of these advantages, geometrically patterning stem cells using stencils may offer greater repeatability from batch-to-batch and person-to-person, an increase in differentiation yield, a faster experimental workflow, and a simpler protocol to communicate and follow. Furthermore, the ability to control where cardiomyocytes arise across a culture well during differentiation could greatly aid the design of electrophysiological assays for drug-screening.

Abstract

Endovascular aneurysm repair (Greenhalgh in N Engl J Med 362(20):1863-1871, 2010) techniques have revolutionized the treatment of thoracic and abdominal aortic aneurysm disease, greatly reducing the perioperative mortality and morbidity associated with open surgical repair techniques. However, EVAR is not free of important complications such as late device migration, endoleak formation and fracture of device components that may result in adverse events such as aneurysm enlargement, need for long-term imaging surveillance and secondary interventions or even death. These complications result from the device inability to withstand the hemodynamics of blood flow and to keep its originally intended post-operative position over time. Understanding the in vivo biomechanical working environment experienced by endografts is a critical factor in improving their long-term performance. To date, no study has investigated the mechanics of contact between device and aorta in a three-dimensional setting. In this work, we developed a comprehensive Computational Solid Mechanics and Computational Fluid Dynamics framework to investigate the mechanics of endograft positional stability. The main building blocks of this framework are: (1) Three-dimensional non-planar aortic and stent-graft geometrical models, (2) Realistic multi-material constitutive laws for aorta, stent, and graft, (3) Physiological values for blood flow and pressure, and (4) Frictional model to describe the contact between the endograft and the aorta. We introduce a new metric for numerical quantification of the positional stability of the endograft. Lastly, in the results section, we test the framework by investigating the impact of several factors that are clinically known to affect endograft stability.

Abstract

Recent advances in image-based modeling and computational fluid dynamics permit the calculation of coronary artery pressure and flow from typically acquired coronary computed tomography (CT) scans. Computed fractional flow reserve is the ratio of mean coronary artery pressure divided by mean aortic pressure under conditions of simulated maximal coronary hyperemia, thus providing a noninvasive estimate of fractional flow reserve (FFRCT) at every point in the coronary tree. Prospective multicenter clinical trials have shown that computed FFRCT improves diagnostic accuracy and discrimination compared to CT stenosis alone for the diagnosis of hemodynamically significant coronary artery disease (CAD), when compared to invasive FFR as the reference gold standard. This promising new technology provides a combined anatomic and physiologic assessment of CAD in a single noninvasive test that can help select patients for invasive angiography and revascularization or best medical therapy. Further evaluation of the clinical effectiveness and economic implications of noninvasive FFRCT are now being explored.

Abstract

Treatment of abdominal aortic aneurysms with high-risk anatomy (neck length <10-15 mm, neck angle >60°) using commercially available devices has become increasingly common with expanding institutional experience. We examined whether placement of approved devices in short angled necks provides acceptable durability at early and intermediate time points.A total of 218 patients (197 men, 21 women) at a single academic center underwent endovascular aneurysm repair (EVAR) with a commercially available device between January 2004 and December 2007. Available medical records, pre- and postoperative imaging, and clinical follow-up were retrospectively reviewed. Patients were divided into those with suitable anatomy (instructions for use, IFU) for EVAR and those with high-risk anatomic aneurysm characteristics (non-IFU).IFU (n = 143) patients underwent repair with Excluder (40%), AneuRx (34%), and Zenith (26%) devices, whereas non-IFU (n = 75) were preferentially treated with Zenith (57%) over Excluder (25%) and AneuRx (17%). Demographics and medical comorbidities between the groups were similar. Operative mortality was 1.4% (2.1% IFU, 0% non-IFU) with mean follow-up of 35 months (range 12-72). Non-IFU patients tended to have larger sac diameters (46.7% ≥60 mm) with shorter (30.7% ≤10 mm), conical (49.3%), and more angled (68% >60°) necks (all p .05).EVAR may be performed safely in high-risk patients with unfavorable neck anatomy using particular commercially available endografts. In our experience, the preferential use of active suprarenal fixation and aggressive use of proximal cuffs is associated with optimal results in these settings. Mid-term outcomes are comparable with those achieved in patients with suitable anatomy using a similar range of EVAR devices. Careful and mandatory long-term follow-up will be necessary to confirm the benefit of treating these high-risk anatomic patients.

Abstract

Stem cell therapies hold great promise for repairing tissues damaged due to disease or injury. However, a major obstacle facing this field is the difficulty in identifying cells of a desired phenotype from the heterogeneous population that arises during stem cell differentiation. Conventional fluorescence flow cytometry and magnetic cell purification require exogenous labeling of cell surface markers which can interfere with the performance of the cells of interest. Here, we describe a non-genetic, label-free cell cytometry method based on electrophysiological response to stimulus. As many of the cell types relevant for regenerative medicine are electrically-excitable (e.g. cardiomyocytes, neurons, smooth muscle cells), this technology is well-suited for identifying cells from heterogeneous stem cell progeny without the risk and expense associated with molecular labeling or genetic modification. Our label-free cell cytometer is capable of distinguishing clusters of undifferentiated human induced pluripotent stem cells (iPSC) from iPSC-derived cardiomyocyte (iPSC-CM) clusters. The system utilizes a microfluidic device with integrated electrodes for both electrical stimulation and recording of extracellular field potential (FP) signals from suspended cells in flow. The unique electrode configuration provides excellent rejection of field stimulus artifact while enabling sensitive detection of FPs with a noise floor of 2 μV(rms). Cells are self-aligned to the recording electrodes via hydrodynamic flow focusing. Based on automated analysis of these extracellular signals, the system distinguishes cardiomyocytes from non-cardiomyocytes. This is an entirely new approach to cell cytometry, in which a cell's functionality is assessed rather than its expression profile or physical characteristics.

Abstract

The purpose of the present study was to investigate whether tanshinone IIA (Tan IIA), one of the major lipophilic components of Salvia miltiorrhiza Bunge, could inhibit the development of elastase-induced experimental abdominal aortic aneurysms (AAAs).Male Sprague-Dawley rats (n = 12/group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from the Tan IIA and control groups underwent intra-aortic elastase perfusion to induce AAAs, and the rats in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg/rat/d). The maximum luminal diameter of the abdominal aorta was measured before and 5, 12, 18, and 24 d after perfusion. The systolic blood pressure was measured twice using the tail cuff technique before administration and death. Aortic tissue samples were harvested at 24 d and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and Miller's elastin-Van Gieson staining.The rats in the control group had significantly increased aortic sizes compared with the sham group after 24 days (P < 0.05), and the Tan IIA group had a significant reduction in aortic size (Tan IIA versus control, P < 0.05) without affecting blood pressure (P > 0.05). The overexpression of matrix metalloproteinase-2, metalloproteinase-9, monocyte chemotactic protein-1, and inducible nitric oxide synthase and the depletion of elastic fibers and vascular smooth muscle cells induced by elastase perfusion were significantly decreased by Tan IIA treatment (P < 0.05).Tan IIA inhibited the development of elastase-induced experimental AAAs by suppressing proteolysis, inflammation, and oxidative stress and preserving vascular smooth muscle cells. It could be a new pharmacologic therapy for AAAs.

Abstract

Vascular ultrasound can provide quick and reliable diagnosis of arterial bleeding but it requires trained and experienced personnel. Development of automated sonographic bleed detection methods would potentially be valuable for trauma management in the field. We propose a detection method that (1) measures blood flow in a trauma victim, (2) determines the victim's expected normal limb arterial flow using a power law biofluid model where flow is proportional to the vessel diameter taken to a power of k and (3) quantifies the difference between measured and expected flow with a novel metric, flow split deviation (FSD). FSD was devised to give a quantitative value for the likelihood of arterial bleeding and validated in human upper extremities. We used ultrasound to demonstrate that the power law with k = 2.75 appropriately described the normal brachial artery bifurcation geometry and adequately determined the expected normal flows. Our metric was then applied to three-dimensional (3-D) computational models of forearm bleeding and on dialysis patients undergoing surgical construction of wrist arteriovenous fistulas. Computational models showed that larger sized arterial defects produced larger flow deviations. FSD values were statistically higher (paired t-test) for arms with fistulas than those without, with average FSDs of 0.41 ± 0.12 and 0.047 ± 0.021 (mean ± SD), respectively. The average of the differences was 0.36 ± 0.12 (mean ± SD).

Abstract

As endovascular treatment of abdominal aortic aneurysms (AAAs) gains popularity, it is becoming possible to treat certain challenging aneurysmal anatomies with endografts relying on suprarenal fixation. In such anatomies, the bare struts of the device may be placed across the renal artery ostia, causing partial obstruction to renal artery blood flow. Computational fluid dynamics (CFD) was used to simulate blood flow from the aorta to the renal arteries, utilizing patient-specific boundary conditions, in three patient models and calculate the degree of shear-based blood damage (hemolysis). We used contrast-enhanced computed tomography angiography (CTA) data from three AAA patients who were treated with a novel endograft to build patient-specific models. For each of the three patients, we constructed a baseline model and endoframe model. The baseline model was a direct representation of the patient's 30-day post-operative CTA data. This model was then altered to create the endoframe model, which included a ring of metallic struts across the renal artery ostia. CFD was used to simulate blood flow, utilizing patient-specific boundary conditions. Pressures, flows, shear stresses, and the normalized index of hemolysis (NIH) were quantified for all patients. The overall differences between the baseline and endoframe models for all three patients were minimal, as measured though pressure, volumetric flow, velocity, and shear stress. The average NIH across the three baseline and endoframe models was 0.002 and 0.004, respectively. Results of CFD modeling show that the overall disturbance to flow caused by the presence of the endoframe struts is minimal. The magnitude of the NIH in all models was well below the accepted design and safety threshold for implantable medical devices that interact with blood flow.

Abstract

An increasing number of patients with abdominal aortic aneurysms are treated using endovascular rather than open surgical techniques. The Vascular Surgery Center, P. Stradins Clinical University Hospital, has the largest worldwide experience using a new type of endoprosthesis, which fills and anchors the device in the aneurysm sac. Within the framework of a clinical trial, the quality-of-life evaluation of patients treated using this type of device was carried out.A cohort study was conducted from 2008 to 2011 comparing the quality of life (QOL) of patients after abdominal aortic aneurysm repair with either the new endovascular treatment method (EVAR) or open surgery (OS). Each group comprised 20 patients, and the quality-of life-evaluation was performed using the SF-36 questionnaire before operation, 1 month after operation, and 1 year after operation.One month after operation, an improved QOL was documented in the EVAR group (47 [SD, 3] in the EVAR group vs. 38 [SD, 3] in the OS group, P<0.001). One year after operation, a significant improvement in QOL persisted although the difference between the groups diminished (48 [SD, 4] in the EVAR group vs. 42 [SD, 3] in the OS group, P<0.001).The patients with abdominal aortic aneurysms who underwent EVAR using the new sac-anchoring endoprosthesis have improved health-related quality of life compared to the patients undergoing open surgical repair. The improvement in quality of life remained slightly better in the EVAR group 1 year after operation.

Abstract

Renal sympathetic hyperactivity is associated with hypertension, a leading cause of mortality worldwide. Renal sympathetic denervation via the Symplicity Catheter System has been shown to decrease blood pressure by 33/11 mmHg by 6 months, with no radiofrequency (RF)-related adverse sequelae visible by CT/MR angiography or renal duplex ultrasound 6 months after the procedure. Here, we present preclinical work predating those clinical results. We performed therapeutic renal sympathetic denervation in a swine animal model to characterize the vascular safety and healing response 6 months after renal denervation therapy.In December 2007, seven domestic swine received a total of 32 radiofrequency ablations via the Symplicity Catheter System and were euthanatized 6 months later. Renal angiography was done before, immediately after, and 6 months after procedure. The renal vessels were examined histologically with H&E and Movat pentachrome stains to identify evidence of vascular and neural injury. The kidneys and urinary system were also examined for evidence of gross and microscopic abnormalities.Renal nerve injury involved primarily nerve fibrosis, replacement of nerve fascicles with fibrous connective tissue, and thickening of the epineurium and perineurium. Renal arterial findings included fibrosis of 10-25% of the total media and underlying adventitia, with mild disruption of the external elastic lamina. No significant smooth muscle hyperplasia or inflammatory components were observed. There was no renal arterial stenosis or thrombosis observed by angiography or histology. No gross or microscopic device-related abnormalities were noted in the kidney, surrounding stroma, or urinary bladder.In a swine model, renal denervation via the Symplicity Catheter System resulted in no clinically significant adverse renal artery or renal findings 6 months after the procedure. This is corroborated by the vascular safety profile demonstrated in subsequent human clinical studies.

Abstract

To determine the risk of aneurysm rupture in patients with persisting proximal type Ia endoleaks following endovascular aneurysm repair (EVAR) in comparison to the risk of rupture of untreated abdominal aortic aneurysms (AAA) of similar size.Among 400 patients who where treated with EVAR from 1996 to 2003 at a single center, 21 (5.3%) patients (13 men; mean age 78.0±5.0 years, range 67-86) with large (≥5.5 cm) aneurysms had imaging evidence of type Ia endoleaks that persisted >10 months (type Ia group) despite secondary endovascular treatment. These patients were compared to 24 untreated AAA patients (17 men; mean age 73.8±5.2 years, range 64-88) with large aneurysms from a separate geographic region with a well-established aneurysm treatment program before EVAR became available (1990-1998).There were no significant differences between the type Ia and the untreated AAA patients with regard to age (79±8 vs. 74±5 years), gender (38% vs. 29% women), baseline aneurysm diameter (6.1±0.7 vs. 6.4±0.9 cm), or length of follow-up (32±23 vs. 29±40 months). During the follow-up period, the rate of aneurysm enlargement was significantly lower in type Ia patients (0.19 cm/y) than in untreated AAA patients (0.54 cm/y, p = 0.03). One (4.8%) patient with a persisting type Ia endoleak and 2-cm aneurysm enlargement (0.8 cm/y) had aneurysm rupture after 2.5 years, while 12 (50%) of the 24 untreated aneurysms ruptured (p = 0.001), which was the primary cause of death in this group. The rupture rate was 1.8 per 100 patient-years in the type Ia group and 20.7 per 100 patient-years in the untreated AAA group. Aneurysm-related mortality was significantly reduced in the type Ia group compared to the untreated AAA group at 36 months (11% vs. 52%, p = 0.004). In the multivariate analysis, factors associated with death were an untreated AAA (odds ratio 97, p = 0.004), female gender (odds ratio 9.7, p = 0.02), and baseline aneurysm size (odds ratio 4.7/cm, p = 0.03).This study suggests that EVAR may reduce the risk of rupture and aneurysm-related death despite the presence of a persisting type Ia endoleak. This finding is limited to patients with aortic endografts that are in good position. The mechanism of protection from rupture is unclear but may be related to reducing the rate of aneurysm enlargement.

Abstract

The ability to stimulate mammalian cells with light has significantly changed our understanding of electrically excitable tissues in health and disease, paving the way toward various novel therapeutic applications. Here, we demonstrate the potential of optogenetic control in cardiac cells using a hybrid experimental/computational technique. Experimentally, we introduced channelrhodopsin-2 into undifferentiated human embryonic stem cells via a lentiviral vector, and sorted and expanded the genetically engineered cells. Via directed differentiation, we created channelrhodopsin-expressing cardiomyocytes, which we subjected to optical stimulation. To quantify the impact of photostimulation, we assessed electrical, biochemical, and mechanical signals using patch-clamping, multielectrode array recordings, and video microscopy. Computationally, we introduced channelrhodopsin-2 into a classic autorhythmic cardiac cell model via an additional photocurrent governed by a light-sensitive gating variable. Upon optical stimulation, the channel opens and allows sodium ions to enter the cell, inducing a fast upstroke of the transmembrane potential. We calibrated the channelrhodopsin-expressing cell model using single action potential readings for different photostimulation amplitudes, pulse widths, and frequencies. To illustrate the potential of the proposed approach, we virtually injected channelrhodopsin-expressing cells into different locations of a human heart, and explored its activation sequences upon optical stimulation. Our experimentally calibrated computational toolbox allows us to virtually probe landscapes of process parameters, and identify optimal photostimulation sequences toward pacing hearts with light.

Abstract

To evaluate the biomechanical and hemodynamic forces acting on the intermodular junctions of a multi-component thoracic endograft and elucidate their influence on the development of type III endoleak due to disconnection of stent-graft segments.Three-dimensional computer models of the thoracic aorta and a 4-component thoracic endograft were constructed using postoperative (baseline) and follow-up computed tomography (CT) data from a 69-year-old patient who developed type III endoleak 4 years after stent-graft placement. Computational fluid dynamics (CFD) techniques were used to quantitate the displacement forces acting on the device. The contact stresses between the different modules of the graft were then quantified using computational solid mechanics (CSM) techniques. Lastly, the intermodular junction frictional stability was evaluated using a Coulomb model.The CFD analysis revealed that curvature and length are key determinants of the displacement forces experienced by each endograft and that the first 2 modules were exposed to displacement forces acting in opposite directions in both the lateral and longitudinal axes. The CSM analysis revealed that the highest concentration of stresses occurred at the junction between the first and second modules of the device. Furthermore, the frictional analysis demonstrated that most of the surface area (53%) of this junction had unstable contact. The predicted critical zone of intermodular stress concentration and frictional instability matched the location of the type III endoleak observed in the 4-year follow-up CT image.The region of larger intermodular stresses and highest frictional instability correlated with the zone where a type III endoleak developed 4 years after thoracic stent-graft placement. Computational techniques can be helpful in evaluating the risk of endograft migration and potential for modular disconnection and may be useful in improving device placement strategies and endograft design.

Abstract

All current aortic endografts depend on proximal and distal fixation to prevent migration. However, migration and rupture can occur, particularly in patients with aortic necks that are short or angulated, or both. We present our initial clinical experience with a new sac-anchoring endoprosthesis designed to anchor and seal the device within the aneurysm sac.The initial worldwide experience using a new endoprosthesis for the treatment of aortic aneurysms (Nellix Endovascular, Palo Alto, Calif) was reviewed. The endoprosthesis consists of dual balloon-expandable endoframes surrounded by polymer-filled endobags designed to obliterate the aneurysm sac and maintain endograft position. Clinical results and follow-up contrast computed tomography (CT) scans at 30 days and 6 and 12 months were reviewed.The endograft was successfully deployed in 21 patients with infrarenal aortic aneurysms measuring 5.7 ± 0.7 cm (range, 4.3-7.4 cm). Two patients with common iliac aneurysms were treated with sac-anchoring extenders that maintained patency of the internal iliac artery. Infusion of 71 ± 37 mL of polymer (range, 19-158 mL) into the aortic endobags resulted in complete aneurysm exclusion in all patients. Mean implant time was 76 ± 35 minutes, with 33 ± 17 minutes of fluoroscopy time and 180 ± 81 mL of contrast; estimated blood loss was 174 ± 116 mL. One patient died during the postoperative period (30-day mortality, 4.8%), and one died at 10 months from non-device-related causes. During a mean follow-up of 8.7 ± 3.1 months and a median of 6.3 months, there were no late aneurysm- or device-related adverse events and no secondary procedures. CT imaging studies at 6 months and 1 year revealed no increase in aneurysm size, no device migration, and no new endoleaks. One patient had a limited proximal type I endoleak at 30 days that resolved at 60 days and remained sealed. One patient has an ongoing distal type I endoleak near the iliac bifurcation, with no change in aneurysm size at 12 months.Initial clinical experience with this novel intrasac anchoring prosthesis is promising, with successful aneurysm exclusion and good short-term results. This new device platform has the potential to address the anatomic restrictions and limitations of current endografts. Further studies with a longer follow-up time are needed.

Abstract

Since the introduction of endovascular aneurysm repair (EVAR), long-term follow-up studies reporting single-device results are scarce. In this study, we focus on EVAR repair with the Talent stent graft (Medtronic, Santa Rosa, Calif).Between July 2000 and December 2007, 365 patients underwent elective EVAR with a Talent device. Patient data were gathered prospectively and evaluated retrospectively. By American Society of Anesthesiologists category, 74% were categories III and IV. Postoperative computed tomography (CT) scanning was performed before discharge, at 3, 12 months, and yearly thereafter. Data are presented according to reporting standards for EVAR.The mean proximal aortic neck diameter was 27 mm (range, 16-36 mm), with a neck length <15 mm in 31% (data available for 193 patients). Deployment of endografts was successful in 361 of 365 patients (99%). Initially, conversion to laparotomy was necessary in four patients. Primary technical success determined by results from computed tomography (CT) scans before discharge was achieved in 333 patients (91%). Proximal type I endoleaks were present in 28 patients (8%) during follow-up, and 14 of these patients needed additional treatment for type I endoleak. The 30-day mortality for the whole Talent group was 1.1% (4 of 365). Follow-up to 84 months is reported for 24 patients. During follow-up, 122 (33%) patients died; in nine, death was abdominal aortic aneurysm (AAA)-related (including 30-day mortality). Kaplan-Meier estimates revealed primary clinical success rates of 98% at 1 year, 93% at 2 years, 88% at 3 years, 79% at 4 years, 64% at 5 years, 51% at 6 years, and 48% at 7 years. Secondary interventions were performed in 73 of 365 patients (20%). Ten conversions for failed endografts were performed. Life-table yearly risk for AAA-related reintervention was 6%, yearly risk for conversion to open repair was 1.1%, yearly risk for total mortality was 8.9%, and yearly risk for AAA-related mortality was 0.8%.Initially, technical success of endovascular aneurysm repair (EVAR) using the Talent endograft is high, with acceptable yearly risk for AAA-related mortality and conversion. However, a substantial amount of mainly endovascular reinterventions is necessary during long-term follow-up to achieve these results.

Abstract

To develop an arterial injury model for testing hemostatic devices at well-defined high and low bleeding rates.A side-hole arterial injury was created in the carotid artery of sheep. Shed blood was collected in a jugular venous reservoir and bleeding rate at the site of arterial injury was controlled by regulating outflow resistance from the venous reservoir. Two models were studied: uncontrolled exsanguinating hemorrhage and bleeding at controlled rates with blood return to maintain hemodynamic stability. Transcutaneous Duplex ultrasound was used to characterize ultrasound signatures at various bleeding rates.A 2.5 mm arterial side-hole resulted in exsanguinating hemorrhage with an initial bleeding rate of 400 ml/min which, without resuscitation, decreased to below 100 ml/min in 5 minutes. After 17 minutes, bleeding from the injury site stopped and the animal had lost 60% of total blood volume. Reinfusion of shed blood maintained normal hemodynamics and both high and low bleeding rates could be maintained without hemorrhagic shock. Bleeding rate at the arterial injury site was held at 395±78 ml/min for 8 minutes, 110±11 ml/min for 15 minutes, and 12±1 ml/min for 12 minutes. Doppler flow signatures at the site of injury were characterized by high peak and end-diastolic flow velocities at the bleeding site which varied with the rate of hemorrhage.We have developed a hemodynamically stable model of acute arterial injury which can be used to evaluate diagnostic and treatment methods focused on control of the arterial injury site.

Abstract

We have developed instrumentation which stimulates and records electrophysiological signals from populations of suspended cells in microfluidic channels. We are employing this instrumentation in a new approach to cell sorting and flow cytometry which distinguishes cells based on their electrophysiology. This label-free approach is ideal for applications where labeling or genetic modification of cells is undesirable, such as in purifying cells for tissue replacement therapies. Electrophysiology is a powerful indicator of phenotype for electrically-excitable cells such as myocytes and neurons. However, extracellular field potential signals are notoriously weak and large stimulus artifacts can easily obscure these signals if care is not taken to suppress them. This is particularly true for suspended cells. Here, we describe a novel microelectrode configuration and the associated instrumentation for suppressing stimulus artifacts and faithfully recovering the extracellular field potential signal. We show that the device is capable of distinguishing cardiomyocytes from non-cardiomyocytes derived from the same stem cell population. Finally, we explain the relationship between extracellular field potentials and the more familiar transmembrane action potential signal, noting the physiologically important features of these signals.

Abstract

To study the role of cell-extracellular matrix (ECM) interactions, microscale approaches provide the potential to perform high throughput assessment of the effect of the ECM microenvironment on cellular function and phenotype. Using a microscale direct writing (MDW) technique, we characterized the generation of multicomponent ECM microarrays for cellular micropatterning, localization and stem cell fate determination. ECMs and other biomolecules of various geometries and sizes were printed onto epoxide-modified glass substrates to evaluate cell attachment by human endothelial cells. The endothelial cells displayed strong preferential attachment to the ECM patterned regions and aligned their cytoskeleton along the direction of the micropatterns. We next generated ECM microarrays that contained one or more ECM components (namely gelatin, collagen IV and fibronectin) and then cultured murine embryonic stem cell (ESCs) on the microarrays. The ESCs selectively attached to the micropatterned features and expressed markers associated with a pluripotent phenotype, such as E-cadherin and alkaline phosphatase, when maintained in growth medium containing leukemia inhibitory factor. In the presence of the soluble factors retinoic acid and bone morphogenetic protein-4 the ESCs differentiated towards the ectodermal lineage on the ECM microarray with differential ECM effects. The ESCs cultured on gelatin showed significantly higher levels of pan cytokeratin expression, when compared with cells cultured on collagen IV or fibronectin, suggesting that gelatin preferentially promotes ectodermal differentiation. In summary, our results demonstrate that MDW is a versatile approach to print ECMs of diverse geometries and compositions onto surfaces, and it is amenable to the generation of multicomponent ECM microarrays for stem cell fate determination.

Abstract

New detection methods for vascular injuries can augment the usability of an ultrasound (US) imager in trauma settings. The goal of this study was to evaluate a potential-detection strategy for internal bleeding that employs a well-established theoretical biofluid model, the power law. This law characterizes normal blood-flow rates through an arterial tree by its bifurcation geometry. By detecting flows that deviate from the model, we hypothesized that vascular abnormalities could be localized. We devised a bleed metric, flow-split deviation (FSD), that quantified the difference between patient and model blood flows at vessel bifurcations. Femoral bleeds were introduced into ten rabbits (∼5 kg) using a cannula attached to a variable pump. Different bleed rates (0% as control, 5%, 10%, 15%, 20%, 25%, and 30% of descending aortic flow) were created at two physiological states (rest and elevated state with epinephrine). FSDs were found by US imaging the iliac arteries. Our bleed metric demonstrated good sensitivity and specificity at moderate bleed rates; area under receiver-operating characteristic curves were greater than 0.95 for bleed rates 20% and higher. Thus, FSD was a good indicator of bleed severity and may serve as an additional tool in the US bleed detection.

Abstract

Endograft migration is usually described as a downward displacement of the endograft with respect to the renal arteries. However, change in endograft position is actually a complex process in three-dimensional (3D) space. Currently, there are no established techniques to define such positional changes over time. The purpose of this study is to determine whether the direction of aortic endograft movement as observed in follow-up computed tomography (CT) scans is related to the directional displacement force acting on the endograft.We quantitated the 3D positional change over time of five abdominal endografts by determining the endograft centroid at baseline (postoperative scan) and on follow-up CT scans. The time interval between CT scans for the 5 patients ranged from 8 months to 8 years. We then used 3D image segmentation and computational fluid dynamics (CFD) techniques to quantitate the pulsatile displacement force (in Newtons [N]) acting on the endografts in the postoperative configurations. Finally, we calculated a correlation metric between the direction of the displacement force vector and the endograft movement by computing the cosine of the angle of these two vectors.The average 3D movement of the endograft centroid was 18 mm (range, 9-29 mm) with greater movement in patients with longer follow-up times. In all cases, the movement of the endograft had significant components in all three spatial directions: Two of the endografts had the largest component of movement in the transverse direction, whereas three endografts had the largest component of movement in the axial direction. The magnitude and orientation of the endograft displacement force varied depending on aortic angulation and hemodynamic conditions. The average magnitude of displacement force for all endografts was 5.8 N (range, 3.7-9.5 N). The orientation of displacement force was in general perpendicular to the greatest curvature of the endograft. The average correlation metric, defined as the cosine of the angle between the displacement force and the endograft centroid movement, was 0.38 (range, 0.08-0.66).Computational methods applied to patient-specific postoperative image data can be used to quantitate 3D displacement force and movement of endografts over time. It appears that endograft movement is related to the magnitude and direction of the displacement force acting on aortic endografts. These methods can be used to increase our understanding of clinical endograft migration.

Abstract

Although repair of large abdominal aortic aneurysms (AAAs) is well accepted, randomized clinical trials have failed to demonstrate benefit for early surgical repair of small aneurysms compared with surveillance. Endovascular repair has been shown to be safer than open surgical repair in patients with large aneurysms, prompting a randomized trial of early endovascular repair vs surveillance in patients with small aneurysms.We randomly assigned 728 patients (13.3% women; mean age, 71 +/- 8 years) with 4 to 5 cm AAAs to early endovascular repair (366 patients) or ultrasound surveillance (362 patients). Rupture or aneurysm-related death and overall mortality in the two groups were compared during a mean follow-up of 20 +/- 12 months.Among patients randomized to treatment, 89% underwent aneurysm repair. Among patients randomized to surveillance, 31% underwent aneurysm repair during the course of the study. After a mean follow-up of 20 +/- 12 months (range, 0-41 months), 15 deaths had occurred in each group (4.1%). The unadjusted hazard ratio (95% confidence interval) for mortality after early endovascular repair was 1.01 (0.49-2.07, P = .98). Aneurysm rupture or aneurysm-related death occurred in two patients in each group (0.6%). The unadjusted hazard ratio was 0.99 (0.14-7.06, P = .99) for early endovascular repair.Early treatment with endovascular repair and rigorous surveillance with selective aneurysm treatment as indicated both appear to be safe alternatives for patients with small AAAs, protecting the patient from rupture or aneurysm-related death for at least 3 years.

Abstract

An 82-year-old female with a history of right carotid endarterectomy with patch closure 12 years prior presents with a pulsatile right neck mass with skin erosion and bleeding. The patient had been previously evaluated but refused the surgical intervention because a median sternotomy was recommended to obtain adequate proximal control. Her aneurysm was successfully repaired using a combination of open and endovascular method. The repair was performed through a right-hand side anterior sternocleidomastoid neck incision, and proximal vascular control was obtained with an 8.5-mm balloon positioned under fluoroscopic guidance via a femoral puncture.

Abstract

The geometry and dynamics of the vena cava are poorly understood and current knowledge is largely based on qualitative data. The purpose of this study is to quantitate the dimensional changes that occur in the infrarenal inferior vena cava (IVC), in response to changes in intravascular volume.IVC dimensions were measured at 1 cm and 5 cm below the renal veins, on serial contrasted computed tomographic (CT) scans, in 30 severely injured trauma patients during hypovolemic (admission) and fluid resuscitated (follow-up) states. Changes in volume of the infrarenal segment were calculated and correlated with changes in IVC diameter and orientation. The orientation of the infrarenal caval segment was quantified as the angulation of the major axis from the horizontal. A representation of the IVC diameter, as would be seen on standard anterior-posterior venographic imaging, was determined by projecting the CT image of the major axis onto a coronal plane. CT representations of venographic diameters were compared with measurements of the true major axis to assess accuracy of venograms for caval sizing and filter selection.All patients had evidence of a collapsed IVC (<15 mm minor axis dimension) on admission. Mean time between admission and follow-up CT was 49.5 (range: 1-202) days. The volume of the infrarenal segment increased more than twofold with resuscitation, increasing from 6.9 +/- 2.2 (range: 3.1-12.4) mL on admission, to 15.7 +/- 5.0 (range: 9.2-28.5) mL on follow-up (P < .01). At both 1 and 5 cm below the renal veins, the IVC expanded anisotropically such that the minor axis expanded up to five times its initial size accommodating 84% of the increased volume of the segment, while only small diameter changes were observed in the major axis accounting for less than 5% of the volume increase (P < .001). Further, the IVC was left-anterior-oblique in all patients, with the major axis 26 degrees off the horizontal on average. This orientation did not change significantly with volume resuscitation (P > 0.5). The obliquity of the IVC resulted in significant underestimation of caval size of up to 6.8 mm, when using the venographic representation for sizing instead of the true major axis (P < 0.001).In response to changes in intravascular volume, the IVC undergoes profound anisotropic dimensional changes, with greater displacement seen in the minor axis. In addition, the IVC is oriented left-anterior oblique and caval orientation is not altered by changes in volume status. IVC obliquity may result in underestimation of caval size by anterior-posterior venogram.

Abstract

Open surgical repair after failed endovascular aneurysm repair (EVAR) usually involves complete endograft removal and replacement with a prosthetic surgical graft. This is associated with significant morbidity and mortality. We have used an alternative strategy focused on limiting the magnitude of surgical repair by preserving the functioning portion of the endograft and avoiding aortic cross-clamping, when possible.Between January 2000 and 2008, patients requiring delayed conversion after EVAR at our institution were managed with (1) complete endograft preservation and external wrap of the aortic neck to secure a proximal seal, or (2) partial endograft removal with interposition grafting from the infrarenal aortic neck to the remaining endograft. Records of all patients were retrospectively reviewed for demographics, operative details, and outcomes.During this time, 12 patients were treated with delayed open surgical conversion. The indication for conversion in all patients was a type I endoleak with aneurysm enlargement not amendable to percutaneous intervention. Mean age was 81 +/- 6.2 years (range, 61-90 years). Average time to conversion was 44.7 months (range, 7-80 months). Complete endograft preservation was attempted in eight patients and was successful in six (75%). The two patients that failed this approach, as well as four additional patients who were not candidates for this approach, underwent partial endograft excision and replacement with an interposition graft sutured to the remaining portion of the stent graft. Complete endograft removal was not required in any patients. There was one post-operative mortality (8.3%) and one significant post-operative morbidity (8.3%). Mean intensive care unit and hospital stays were 2.8 +/- 3.9 days (range, 1-15 days) and 8.4 +/- 5.8 days (range, 3-26 days), respectively.Open surgical repair of failed EVAR can be accomplished with preservation of all or a significant portion of the endograft in most patients. This may limit the magnitude of the repair procedure and may reduce morbidity and mortality.

Abstract

To examine the 4-year outcomes from Carotid Revascularization using Endarterectomy or Stenting Systems (CaRESS) in light of the current reimbursement guidelines for carotid artery stenting (CAS) from the Centers for Medicare and Medicaid Services (CMS).CaRESS was designed as a prospective, nonrandomized comparative cohort study of a broad-risk population of symptomatic and asymptomatic patients with carotid stenosis. In all, 397 patients (247 men; mean age 71 years, range 43-89) were enrolled and underwent carotid endarterectomy (CEA; n = 254) or protected CAS (n = 143). More than 90% of patients had >75% stenosis; two thirds were asymptomatic. The primary endpoints included (1) all-cause mortality, (2) any stroke, and (3) myocardial infarction (MI), as well as the composite endpoints of (4) death and any nonfatal stroke and (5) death, nonfatal stroke, and MI. The secondary endpoints were restenosis, repeat angiography, and carotid revascularization. All patients were classified with respect to surgical risk, symptom status, and stenosis grade based on criteria published by the CMS. In addition, separate analyses were performed comparing genders and octogenarians to those <80 years old.No significant differences in the primary outcome measures were found between the CEA and CAS groups in the 4-year analysis. The incidences of any stroke at 4 years were 9.6% for CEA and 8.6% for CAS (p = 0.444); when combined with death, the composite death/nonfatal stroke rates were 26.5% for CEA versus 21.8% for CAS (p = 0.361). The composite endpoint of death, nonfatal stroke, and MI at 4 years was 27.0% in CEA versus 21.7% in CAS (p = 0.273) patients. The secondary endpoints of restenosis (p = 0.014) and repeat angiography (p = 0.052) were higher in the CAS arm. There were no differences in any of the subgroups stratified according the CMS guidelines or in the gender comparison. Four-year incidences of death/nonfatal stroke and death/nonfatal stroke/MI were higher in the CEA arm among patients <80 years of age (p = 0.049 and p = 0.030, respectively). There were no significant differences between these incidences in the octogenarian subgroup.The risk of death or nonfatal stroke 4 years following CAS with distal protection is equivalent to CEA in a broad category of patients with carotid stenosis. There were no significant differences in stroke or mortality rates between high-risk and non-high-risk patients and no differences in outcomes between symptomatic and asymptomatic patients. After 4 years, CAS had a 2-fold higher restenosis rate compared to CEA. The risk of death/stroke or death/stroke/MI appears to be higher following CEA than CAS among patients <80 years of age, yet there is no statistically significant relationship between death, stroke, or MI among octogenarians.

Abstract

Chronic mesenteric ischemia is a rare disorder that has traditionally been treated with open surgical revascularization (OR). Endovascular revascularization (ER) has recently gained popularity as an alternative modality of treatment; however, OR is still predominantly used. This study aimed at comparing the outcomes of these two treatment modalities. The literature was searched using the MEDLINE database through the PubMed search engine for relevant articles that compared the outcomes after OR and ER for chronic mesenteric ischemia. Review of the selected articles revealed that patients had lower postoperative mortality and morbidity, and shorter intensive care unit and hospital stay after ER. However, early and long-term symptomatic relief and significantly lower restenosis rate were characteristic of OR. Although no level 1 evidence governs the treatment of chronic mesenteric ischemia, the durability and efficacy of OR is such that this modality should remain the procedure of choice for patients who are fit or whose fitness could be improved before surgery. For unfit patients, or those with short life expectancy, ER is preferable owing to its minimally invasive nature and reduced postoperative mortality and morbidity. Randomized controlled studies are needed to compare the long-term durability and efficacy of ER to those of OR.

Abstract

To determine the effect of curvature on the magnitude and direction of displacement forces acting on aortic endografts in 3-dimensional (3D) computational models.A 3D computer model was constructed based on magnetic resonance angiography data from a patient with an infrarenal aortic aneurysm. Computational fluid dynamics tools were used to simulate realistic flow and pressure conditions of the patient. An aortic endograft was deployed in the model, and the displacement forces acting on the endograft were calculated and expressed in Newtons (N). Additional models were created to determine the effects of reducing endograft curvature, neck angulation, and iliac angulation on displacement forces.The aortic endograft had a curved configuration as a result of the patient's anatomy, with curvature in the anterolateral direction. Total displacement force acting on the endograft was 5.0 N, with 28% of the force in a downward (caudal) direction and 72% of the force in a sideways (anterolateral) direction. Elimination of endograft curvature (planar graft configuration) reduced total displacement force to 0.8 N, with the largest component of force (70%) acting in the sideways direction. Straightening the aortic neck in the curved endograft configuration reduced the total force acting on the endograft to 4.2 N, with a reduction of the sideways component to 55% of the total force. Straightening the iliac limbs of the endograft reduced the total force acting on the endograft to 2.1 N but increased the sideways component to 91% of the total force.The largest component of the force acting on the aortic endograft is in the sideways direction, with respect to the blood flow, rather than in the downward (caudal) direction as is commonly assumed. Increased curvature of the aortic endograft increases the magnitude of the sideways displacement force. The degree of angulation of the proximal and distal ends of the endograft influence the magnitude and direction of displacement force. These factors may have a significant influence on the propensity of endografts to migrate in vivo.

Abstract

To assess 3-dimensional (3D) pulsatile displacement forces (DF) acting on thoracic endografts using 3D computational techniques.A novel computational method to quantitate the pulsatile 3D flow and pressure fields and aortic wall dynamics in patient-specific anatomical models based on cardiac-gated computed tomography (CT) scans was used to construct simulations of the proximal and mid-descending thoracic aorta. Endografts of varying lengths and diameters were implanted in these patient-specific models. The magnitude and direction of the DF vector were calculated and expressed in Newtons (N). This DF included the effects of both the pressure and shearing stresses of blood.The magnitude of DF increased with endografts of increasing diameter and length. A 36-mm endograft in the mid-descending aorta had a mean DF of 21.7 N with a peak systolic DF of 27.8 N and an end-diastolic DF of 16.7 N. Conversely, a 30-mm endograft in the proximal descending aorta had a mean DF of 14.9 N, with peak systolic and end-diastolic DFs of 18.9 and 11.5, respectively. The orientation of the DF acting on the endograft varied depending on aortic angulation and tortuosity; in general, the vector was perpendicular to the greater curvature of the endograft rather than along the downstream longitudinal centerline axis of the aorta as is commonly believed. The DF vector pointed primarily in the cranial direction for the proximal descending endograft and in the sideways direction for the mid-descending endograft simulation. Furthermore, it was shown that elevated pressure plays an important role in the magnitude and direction of DF; an increase in mean blood pressure resulted in an approximately linearly proportional increase in DF.The orientation of the DF varies depending on curvature and location of the endograft, but in all instances, it is in the cranial rather than caudal direction on axial imaging. This is counter to the intuitive notion that displacement forces act in the downward direction of blood flow. Therefore, we postulate that migration of thoracic endografts may be different from abdominal endografts since it may involve upward rather than downward movement of the graft. Computational methods can enhance the understanding of the magnitude and orientation of the loads experienced in vivo by thoracic aortic endografts and therefore improve their design and performance.

Abstract

This study investigated the importance of iliac fixation to secure endograft fixation.Computed tomography (CT) scans of patients who underwent endovascular aneurysm repair with an endoprosthesis of great columnar strength (Talent stent graft) were analysed retrospectively. Patients were enrolled consecutively between June 2000 and January 2007 and prospectively followed up with serial CT imaging. The superior mesenteric artery was used as a reference point to determine endograft migration (centerline endograft displacement of >or=10mm). Proximal and distal fixation lengths were defined as the length of the endograft that was in full apposition to the aortic neck or common iliac arteries, respectively.Proximal endograft migration occurred in 32 of 154 patients (21%) at a follow-up duration of 32+/-14 months; 13 migrations required treatment (8%). Migration was more frequent in patients treated with aorto-uniiliac devices than bifurcation devices (p<0.008). The migrator and non-migrator groups had similar demographic and abdominal aortic aneurysm (AAA) characteristics. The migrator group had significantly shorter proximal (30+/-12 mm vs. 41+/-13 mm, P<0.001) and distal endograft fixation lengths (31+/-18 mm vs. 47+/-15 mm, P<0.001). By multivariate regression analysis, proximal and distal endograft fixations were significant predictors for endograft migration at follow-up (P<0.001).Iliac endograft fixation, along with proximal fixation, is a significant predictor for endograft migration.

Abstract

Ruptured abdominal aortic aneurysm (RAAA) is the most common and devastating complication affecting a patient with abdominal aortic aneurysm (AAA). Despite advances in surgery and critical care, the mortality rate associated with RAAA remains largely unchanged. Emergency open repair is the gold standard conventional treatment of RAAA but is associated with a high mortality rate. The physiologic challenges associated with general anaesthetic induction such as loss of the sympathetic vasoconstrictor tone with consequent hypotension, and the anatomic challenges associated with external aortic cross-clamping such as calcification, friability, or poor visualisation of the aneurysm neck, have led to the adoption of endovascular techniques in the surgical treatment of RAAA. Promising results of endovascular repair of ruptured abdominal aortic aneurysm (REVAR) have been reported. In addition, the provision of endovascular aortic control by inflating a compliant aortic occlusion balloon (AOB) proximal to the ruptured aneurysm, as an internal aortic clamp, has been successfully used in haemodynamically unstable patients undergoing either REVAR or emergency open repair of RAAA. An AOB is inserted under local anaesthesia and can be introduced through either the transbrachial or the transfemoral routes, each with its own advantages and disadvantages. This review aimed at providing an up-to-date overview of the current knowledge concerning endovascular proximal aortic control using an AOB with emphasis on the rationale, position, benefits, and drawbacks of its use.

Abstract

We report the first utilization of time-resolved three-dimensional phase contrast magnetic resonance imaging, termed 4D flow, to image a type I endoleak after endovascular aneurysm repair. The combination of 4D flow and a traditional magnetic resonance angiogram can aid in the accurate detection and characterization of endoleaks by combining the three-dimensional resolution of cross-sectional imaging with the temporally resolved velocity data of Doppler ultrasound.

Abstract

Ruptured abdominal aortic aneurysm (AAA) is one of the most fatal surgical emergencies, with an overall mortality rate of 90%. Most AAAs rupture into the retroperitoneal cavity, which results in the classical triad of pain, hypotension, and a pulsatile mass. However, this triad is seen in only 25-50% of patients, and many patients with ruptured AAA are misdiagnosed. It is likely that different sites of rupture of AAA determine a variety of common and uncommon clinical presentations, the recognition of which can save many lives. This article reviews the different sites of rupture of infrarenal AAA and explores the evidence behind the various clinical presentations seen in patients with ruptured AAA.

Abstract

We developed a novel method using anatomic markers along the thoracic aorta to accurately quantify longitudinal and circumferential cyclic strain in nondiseased thoracic aortas during the cardiac cycle and to compute age-related changes of the human thoracic aorta.Changes in thoracic aorta cyclic strains were quantified using cardiac-gated computed tomography image data of 14 patients (aged 35 to 80 years) with no visible aortic pathology (aneurysms or dissection). We measured the diameter and circumferential cyclic strain in the arch and descending thoracic aorta (DTA), the longitudinal cyclic strain along the DTA, and changes in arch length and motion of the ascending aorta relative to the DTA. Diameters were computed distal to the left coronary artery, proximal and distal to the brachiocephalic trunk, and distal to the left common carotid, left subclavian, and the first and seventh intercostal arteries. Cyclic strains were computed using the Green-Lagrange strain tensor. Arch length was defined along the vessel centerline from the left coronary artery to the first intercostal artery. The length of the DTA was defined along the vessel centerline from the first to seventh intercostal artery. Longitudinal cyclic strain was quantified as the difference between the systolic and diastolic DTA lengths divided by the diastolic DTA length. Comparisons were made between seven younger (age, 41 +/- 7 years; 5 men) and seven older (age, 68 +/- 6 years; 5 men) patients.The average increase of diameters of the thoracic aorta was 14% with age from the younger to the older (mean age, 41 vs 68 years) group. The average circumferential cyclic strain of the thoracic aorta decreased by 55% with age from the younger to the older group. The longitudinal cyclic strain decreased with age by 50% from the younger to older group (2.0% +/- 0.4% vs 1.0% +/- 1%, P = .03). The arch length increased by 14% with age from the younger to the older group (134 +/- 17 mm vs 152 +/- 10 mm, P = .03).The thoracic aorta enlarges circumferentially and axially and deforms significantly less in the circumferential and longitudinal directions with increasing age. To our knowledge, this is the first quantitative description of in vivo longitudinal cyclic strain and length changes for the human thoracic aorta, creating a foundation for standards in reporting data related to in vivo deformation and may have significant implications in endoaortic device design, testing, and stability.

Abstract

Endovascular devices have been designed by trial and error, with bench and animal testing followed by human clinical trials to determine whether the devices are safe and effective. Despite remarkable advances over the past 15 years, there are persistent concerns regarding the long-term durability of endovascular devices. This may be due to deficiencies in device design, which has lagged behind other industries in adopting computational methods that are now routinely used to design, develop, and test new aircraft and automobiles. Similar computational design and failure mode simulations that evaluate performance under stress conditions have not been widely applied in the development of endovascular devices. Advances in medical imaging and computational modeling now allow simulation of physiological conditions in patient-specific 3-dimensional vascular models, which can provide a framework to design and test the next generation of endovascular devices. This modeling will allow the prospective design of devices that can withstand the force variations in the cardiovascular system that occur during bending, coughing, and varying degrees of exercise, as well as the extremes encountered during sudden impact in contact sports. Utilization of computational design methodology that takes into consideration the physiology of the cardiovascular system will improve future endovascular devices so that they are safer and more effective and durable.

Abstract

Acute mesenteric ischaemia is a catastrophic abdominal emergency with an extremely high mortality rate. This article discusses the aetiology, diagnosis and treatment of acute mesenteric ischaemia with emphasis on avoidance of common errors that contribute to the poor outcome inherent to this condition.

Abstract

Acute aortic dissection is one of the most fatal acute cardiovascular disorders that has challenged physicians and surgeons for decades. This article provides an up-to-date overview of the aetiology, pathophysiology, diagnosis and treatment of this condition.

Abstract

To determine the safety and performance of a new inferior vena cava (IVC) filter in an ovine model and evaluate the retrievability at 5 weeks.The Crux Vena Cava Filter (VCF) is composed of 2 nitinol spiral supports with a polymeric filter suspended between them. Retrieval tails on each end facilitate retrieval. Twelve filters were placed in the infrarenal IVCs of 12 sheep. The vessels were imaged pre and post deployment to assess acute device performance. At 5 weeks, the vessels were re-imaged to evaluate continued device performance and vessel integrity. Nine of 12 filters were retrieved, and the animals were returned to their housing. The other 3 animals were sacrificed, and the filters and vessels were processed for gross and histological examination. At 9 weeks, 4 weeks after filter retrieval, vessel integrity of the remaining 9 animals was again assessed under fluoroscopy. The animals were sacrificed, and the IVCs were explanted for study.All 12 filters were implanted without complications at the intended deployment site and remained fixed over the implantation period. At 5 weeks, the filters intended for recovery were successfully retrieved, with a mean capture time of 9.6+/-13.7 minutes. There were no complications during the 4-week follow-up after filter retrieval. Post-retrieval imaging at 5 and 9 weeks showed no visible signs of vessel wall damage. Histological study of 3 explanted vessels and filters revealed slight neointima encapsulation of the filter elements and minimal incorporation. Gross examination of the post-retrieval vessel walls after the 4-week healing period showed minimal superficial vessel damage; histology showed minimal residual signs of hemorrhage, with little to no inflammatory reaction.The Crux VCF was deployed and safely retrieved without incident at 5 weeks in an animal model. There was no significant damage seen to the IVCs 1 month after filter retrieval.

Abstract

Changes in arterial wall composition and function underlie all forms of vascular disease. The fundamental structural and functional unit of the aortic wall is the medial lamellar unit (MLU). While the basic composition and organization of the MLU is known, three-dimensional (3D) microstructural details are tenuous, due (in part) to lack of three-dimensional data at micro- and nano-scales. We applied novel electron and confocal microscopy techniques to obtain 3D volumetric information of aortic medial microstructure at micro- and nano-scales with all constituents present. For the rat abdominal aorta, we show that medial elastin has three primary forms: with approximately 71% of total elastin as thick, continuous lamellar sheets, 27% as thin, protruding interlamellar elastin fibers (IEFs), and 2% as thick radial struts. Elastin pores are not simply holes in lamellar sheets, but are indented and gusseted openings in lamellae. Smooth muscle cells (SMCs) weave throughout the interlamellar elastin framework, with cytoplasmic extensions abutting IEFs, resulting in approximately 20 degrees radial tilt (relative to the lumen surface) of elliptical SMC nuclei. Collagen fibers are organized as large, parallel bundles tightly enveloping SMC nuclei. Quantification of the orientation of collagen bundles, SMC nuclei, and IEFs reveal that all three primary medial constituents have predominantly circumferential orientation, correlating with reported circumferentially dominant values of physiological stress, collagen fiber recruitment, and tissue stiffness. This high resolution three-dimensional view of the aortic media reveals MLU microstructure details that suggest a highly complex and integrated mural organization that correlates with aortic mechanical properties.

Abstract

It is commonly assumed that the aortic wall deforms uniformly and has uniform wall thickness about the circumference. The purpose of this study was to evaluate the aortic wall motion and thickness in the infrarenal aortic neck of patients with abdominal aortic aneurysms who were undergoing endovascular repair (EVAR) and to compare the dynamic measurements of intravascular ultrasonography with the static measurements of computed tomographic angiography (CTA).A total of 25 patients were evaluated before surgery with CTA and three-dimensional reconstructions on a Vitrea workstation, followed by intraoperative assessment of the proximal aortic neck with intravascular ultrasonography (IVUS) before EVAR. Infrarenal aortic neck dimensions on CTA were obtained at 1-mm intervals, but for the purposes of this study all dimensions on CTA were obtained 1 cm below the lowest renal artery. IVUS analysis of the proximal aortic neck was obtained with a 10-second recorded data loop of aortic wall motion. A Digital Imaging and Communications in Medicine viewer was used to view the recorded loop of aortic movement, and each image was captured and then evaluated with a SCION PCI Frame Grabber to determine aortic dimensions and wall thickness. IVUS diameters (250 measurements of each aorta) were recorded through a full continuous cardiac cycle from the epicenter of the lumen (maintaining the left renal vein in its normal anatomic configuration) in an anteroposterior (AP) direction in the area of greatest wall movement and 90 degrees perpendicular to this direction (lateral movement).There was significant variation in infrarenal aortic wall movement about the circumference, with 1.7 +/- 0.6 mm (range, 0.6-2.7 mm) displacement in the AP direction and 0.9 +/- 0.5 mm (range, 0.3-1.5 mm) displacement in the lateral direction (P < .001). Aortic wall thickness was greater in the region of increased AP wall motion than in the area of lesser lateral wall motion (2.3 +/- 0.6 mm vs 1.2 +/- 0.3 mm; P < .001). There was no difference between the IVUS and CTA aortic neck measurements (25.5 vs 25.6 mm; not significant) during the midpoint of the cardiac cycle of IVUS. However, at peak systole, IVUS recorded a greater diameter than CTA (26.4 vs 25.6 mm; P < .001), and at end-diastole, IVUS recorded a smaller diameter than CTA (24.7 vs 25.6 mm; P = .01).The infrarenal neck of aortic aneurysms deforms anisotropically during the cardiac cycle. The greatest displacement is in the AP direction and corresponds with a significantly greater wall thickness in this area. The magnitude of cyclic change in aortic diameter can be as high as 11%. Further evaluation of proximal aortic neck wall motion after EVAR is warranted to determine the interaction of various stent designs and the aortic wall.

Abstract

Therapeutic effects from injection of stem cells are often hampered by acute donor cell death as well as migration away from damaged areas. This is likely due to the fact that injected cells do not have the physical and biochemical cues for ordered engrafment. Here we evaluate 3 common biomatrices (Matrigel, Collagen I, Purmatrix) that has the potential of providing suitable scaffolds needed to enhance stem cell survival. The longitudinal fate of transplanted stem cells was monitored by reporter imaging techniques.

Abstract

To evaluate the role of iliac fixation in preventing migration of suprarenal and infrarenal aortic endografts.Quantitative image analysis was performed in 92 patients with infrarenal aortic aneurysms (76 men and 16 women) treated with suprarenal (n = 36) or infrarenal (n = 56) aortic endografts from 2000 to 2004. The longitudinal centerline distance from the superior mesenteric artery to the top of the stent graft was measured on preoperative, postimplantation, and 1-year three-dimensional computed tomographic scans, with movement more than 5 mm considered to be significant. Aortic diameters were measured perpendicular to the centerline axis. Proximal and distal fixation lengths were defined as the lengths of stent-graft apposition to the aortic neck and the common iliac arteries, respectively.There were no significant differences in age, comorbidities, or preoperative aneurysm size (suprarenal, 6.0 cm; infrarenal, 5.7 cm) between the suprarenal and infrarenal groups. However, the suprarenal group had less favorable aortic necks with a shorter length (13 vs 25 mm; P < .0001), a larger diameter (27 vs 24 mm; P < .0001), and greater angulation (19 degrees vs 11 degrees ; P = .007) compared with the infrarenal group. The proximal aortic fixation length was greater in the suprarenal than in the infrarenal group (22 vs 16 mm; P < .0001), with the top of the device closer to the superior mesenteric artery (8 vs 21 mm; P < .0001) as a result of the 15-mm uncovered suprarenal stent. There was no difference in iliac fixation length between the suprarenal and infrarenal groups (26 vs 25 mm; P = .8). Longitudinal centerline stent graft movement at 1 year was similar in the suprarenal and infrarenal groups (4.3 +/- 4.4 mm vs 4.8 +/- 4.3 mm; P = .6). Patients with longitudinal centerline movement of more than 5 mm at 1 year or clinical evidence of migration at any time during the follow-up period comprised the respective migrator groups. Suprarenal migrators had a shorter iliac fixation length (17 vs 29 mm; P = .006) and a similar aortic fixation length (23 vs 22 mm; P > .999) compared with suprarenal nonmigrators. Infrarenal migrators had a shorter iliac fixation length (18 vs 30 mm; P < .0001) and a similar aortic fixation length (14 vs 17 mm; P = .1) compared with infrarenal nonmigrators. Nonmigrators had closer device proximity to the hypogastric arteries in both the suprarenal (7 vs 17 mm; P = .009) and infrarenal (8 vs 24 mm; P < .0001) groups. No migration occurred in either group in patients with good iliac fixation. Multivariate logistic regression analysis revealed that iliac fixation, as evidenced by iliac fixation length (P = .004) and the device to hypogastric artery distance (P = .002), was a significant independent predictor of migration, whereas suprarenal or infrarenal treatment was not a significant predictor of migration. During a clinical follow-up period of 45 +/- 22 months (range, 12-70 months), there have been no aneurysm ruptures, abdominal aortic aneurysm-related deaths, or surgical conversions in either group.Distal iliac fixation is important in preventing migration of both suprarenal and infrarenal aortic endografts that have longitudinal columnar support. Secure iliac fixation minimizes the risk of migration despite suboptimal proximal aortic neck anatomy. Extension of both iliac limbs to cover the entire common iliac artery to the iliac bifurcation seems to prevent endograft migration.

Abstract

The appropriate size threshold for endovascular repair of small abdominal aortic aneurysms (AAA) is unclear. We studied the outcome of endovascular aneurysm repair (EVAR) as a function of preoperative aneurysm diameter to determine the relationship between aneurysm size and long-term outcome of endovascular repair.We reviewed the results of 923 patients treated in a prospective, multicenter clinical trial of EVAR. Small aneurysms were defined according to two size thresholds of 5.5 cm and 5.0 cm. Two-way analysis was used to compare patients with small aneurysms (<5.5 cm, n = 441) to patients with large aneurysms (> or =5.5 cm, n = 482). An ordered three-way analysis was used to compare patients with small AAA (<5.0 cm, n = 145), medium AAA (5.0 to 5.9 cm, n = 461), and large AAA (> or =6.0 cm, n = 317). The primary outcome measures of rupture, AAA-related death, surgical conversion, secondary intervention, and survival were compared using Kaplan-Meier estimates at 5 years.Median aneurysm size was 5.5 cm. The two-way comparison showed that 5 years after EVAR, patients with small aneurysms (<5.5 cm) had a lower AAA-related death rate (1% vs 6%, P = .006), a higher survival rate (69% vs 57%, P = .0002), and a lower secondary intervention rate (25% vs 32%, P = .03) than patients with large aneurysms (> or =5.5 cm). Three-way analysis revealed that patients with small AAAs (<5.0 cm) were younger (P < .0001) and were more likely to have a family history of aneurysm (P < .05), prior coronary intervention (P = .003), and peripheral occlusive disease (P = .008) than patients with larger AAAs. Patients with smaller AAAs also had more favorable aortic neck anatomy (P < .004). Patients with large AAAs were older (P < .0001), had higher operative risk (P = .01), and were more likely to have chronic obstructive pulmonary disease (P = .005), obesity (P = .03), and congestive heart failure (P = .004). At 5 years, patients with small AAAs had better outcomes, with 100% freedom from rupture vs 97% for medium AAAs and 93% for large AAAs (P = .02), 99% freedom from AAA-related death vs 97% for medium AAAs and 92% for large AAAs (P = .02) and 98% freedom from conversion vs 92% for medium AAAs and 89% for large AAAs (P = .01). Survival was significantly improved in small (69%) and medium AAAs (68%) compared to large AAAs (51%, P < .0001). Multivariate Cox proportional hazards modeling revealed that aneurysm size was a significant independent predictor of rupture (P = .04; hazard ratio [HR], 2.195), AAA-related death (P = .03; HR, 2.007), surgical conversion (P = .007; HR, 1.827), and survival (P = .001; HR, 1.351). There were no significant differences in secondary intervention, endoleak, or migration rates between small, medium, and large AAAs.Preoperative aneurysm size is an important determinant of long-term outcome following endovascular repair. Patients with small AAAs (<5.0 cm) are more favorable candidates for EVAR and have the best long-term outcomes, with 99% freedom from AAA death at 5 years. Patients with large AAAs (> or =6.0 cm) have shorter life expectancy and have a higher risk of rupture, surgical conversion, and aneurysm-related death following EVAR compared to patients with smaller aneurysms. Nonetheless, 92% of patients with large AAAs are protected from AAA-related death at 5 years. Patients with AAAs of intermediate size (5 to 6 cm) represent most of the patients treated with EVAR and have a 97% freedom from AAA-related death at 5 years.

Abstract

To test the hypothesis that a level of chemical and electrical stimulation exists that allows differentiation of progenitor cells into organized contracting myocytes.A custom-made bioreactor with the capability of delivering electrical pulses of varying field strengths, widths, and frequencies was constructed. Individual chambers of the bioreactor allowed continuous electrical stimulation of cultured cells under microscopic observation. On day 0, 1% dimethylsulfoxide (DMSO), known to differentiate cells into myocytes, was added to P19 progenitor cells. Additionally, for the next 22 days, electrical pulses of varying field strengths (0-3 V/cm), widths (2-40 ms), and frequencies (10-25 Hz) were continuously applied. On day 5, the medium containing DMSO was exchanged with regular medium, and the electrical stimulation was continued. From days 6-22, the cells were visually assessed for signs of viability, contractility, and organization.P19 cells remained viable with pulsed electrical fields <3 V/cm, pulse widths <40 ms, and pulse frequencies from 10 to 25 Hz. On day 12, the first spontaneous contractions were observed. For individual colonies, local synchronization and organization occurred; multiple colonies were synchronized with externally applied electrical fields.P19 progenitor cells progress to organized contracting myocytes after chemical and electrical stimulation. Incorporation of such cells into existing methods of producing endothelial cells, fibroblasts, and scaffolds may allow production of improved tissue-engineered vascular grafts.

Abstract

Secure proximal fixation of endografts to the infrarenal aortic neck is known to be important in the short- and long-term success of endovascular aneurysm repair. We sought to determine the relative importance of distal iliac fixation in preventing endograft migration and adverse clinical events after endovascular aneurysm repair.We reviewed the outcome of 173 patients treated from 1996 to 2003 at Stanford University Medical Center with an externally supported stent graft. Quantitative image analysis of the postimplantation computed tomography scan was performed to determine the proximal aortic and distal iliac fixation lengths and the proximity the distal end of the stent graft to the iliac bifurcation. Subsequent follow-up computed tomography scans were reviewed for evidence of stent graft migration. Patients were grouped according to good (>15 mm), intermediate, or bad (<10 mm) aortic fixation and good (iliac fixation length > or =25 mm and iliac limbs <10 mm from iliac bifurcation), intermediate, or bad (<25-mm fixation length) iliac fixation.Stent graft migration of 10 mm or more was seen in 17 patients (10%) during the 23 +/- 19-month follow-up period. Patients with no migration had a greater iliac fixation length (30 +/- 12 mm) than those with migration (22 +/- 8 mm; P = .01), and the distal ends of the iliac limbs were closer to the iliac bifurcation (15 +/- 12 mm) than in patients with migration (25 +/- 10 mm; P < .001). Patients with no migration also had a greater proximal aortic fixation length (23 +/- 12 mm) than migration patients (13 +/- 7 mm; P = .001). There were no migrations among patients with good iliac fixation whether aortic fixation was good, intermediate, or bad (0/63; 0%). Among patients with bad/intermediate iliac and good aortic fixation, there were 5 (9%) of 58 patients had migrations. Patients with both bad/intermediate iliac and bad/intermediate aortic fixation had the highest migration rate (12/52; 23%). Cox proportional hazards regression modeling revealed that the significant factors predicting migration were poor proximity of the distal end of the iliac limbs to the iliac bifurcation (odds ratio 17.2; P = .01) and aortic fixation length (odds ratio 2.0; p = 0.007 for each centimeter). Iliac extender modules were placed in 9 patients with bad iliac fixation and migration, with no further migration during a mean follow-up of 12 months. Patients with good iliac and aortic fixation and no endoleak on the initial postprocedure computed tomography scan (n = 43) had no migrations, secondary procedures, or adverse clinical events over a 2-year follow-up period.Iliac fixation, along with proximal aortic fixation, is an important factor in preventing the migration of stent grafts that have longitudinal columnar support. Patients with good iliac fixation did not experience migration even in the presence of suboptimal proximal aortic fixation. Close proximity of the distal end of the stent graft to the iliac bifurcation seems to provide stability against migration.

Abstract

Currently available vascular grafts have been limited by variable patency rates, material availability, and immunological rejection. The creation of a tissue-engineered vascular graft (TEVG) from autologous stem cells would potentially overcome these limitations. As a first step in creating a completely autologous TEVG, our objective was to develop a novel system for culturing undifferentiated mouse embryonic stem cells (mESC) in a three-dimensional (3D) configuration and under physiological pulsatile flow and pressure conditions.A bioreactor was created to provide pulsatile conditions to a specially modified four-well Labtek Chamber-Slide culture system. Undifferentiated mESC were either suspended in a 3D Matrigel matrix or suspended only in cell-culture media within the culture system. Pulsatile conditions were applied to the suspended cells and visualized by video microscopy.Undifferentiated mESC were successfully embedded in a 3D Matrigel matrix and could withstand physiological pulsatile conditions. Video microscopy demonstrated that the mESC in the 3D matrix were constrained to the wells of the culture system, moved in unison with the applied flows, and were not washed downstream; this was in contrast to the mESC suspended in media alone.Undifferentiated mESC can be grown in 3D and under pulsatile conditions. We will use these results to study the effects of long-term pulsatile conditions on the differentiation of mESC into endothelial cells, smooth muscle cells, and fibroblast cells with the long-term goal of creating a completely autologous TEVG.

Abstract

Problems of displacement, poor healing, degradation of the polymers and corrosion of the metallic frame in endovascular devices still require in-depth investigations. As the tissues and the foreign materials are in close contact, it is of paramount importance to efficiently investigate the interfaces between them. Inclusion in polymethymethacrylate (PMMA) permits us to obtain thin slides and preserve the capacity to perform the appropriate stainings. An AneuRx prosthesis was harvested in bloc with the surrounding tissues at the autopsy of a patient 25 months post deployment in a 5.7 cm diameter AAA and sectioned in the direction of the blood flow in two halves. A cross-section of the encapsulated distal segment together with the surrounding aneuryshmal sac was embedded in polymethylmethacrylate (PMMA). Further to complete polymerization, slices of the specimen were cut on a precision banding saw under coolant. They were affixed onto methacrylate slides with a UV cured adhesive. Binding and polishing were done on a numeric grinder and slices 25 to 30 microm in thickness were stained with toluidine blue prior to observation in light microscopy. Additional slices were prepared for scanning electron microscopy and X-ray energy dispersive spectrometry for determination of the elemental composition of the Nitinol stent. The aortic wall did not demonstrate complete integrity along with its circumference. Some areas of rupture were noted. The content of the sac was heavily shrunk and was mostly acellular. The walls of the device were very well encapsulated. The PMMA embedding permitted the polyester wall, the Nitinol wire and the collagen to keep in close contact. Scanning electron microscopy involved backscattered electrons and confirmed the corrosion the Nitinol wire at the boundary with living tissues. Based upon the results obtained, we believe that PMMA embedding is the most appropriate method to process endovascular devices for histological and material investigation. Needless to say, that paraffin embedding would have not been feasible for such a big size specimen involving different materials.

Abstract

Information that can be obtained by magnetic resonance imaging (MRI) of explanted endovascular devices must be validated as this method is non-destructive. Histology of such a device together with its encroached tissues can be elegantly performed after polymethymethacrylate (PMMA) embedding, but this approach requires destruction of the specimen. The issue is therefore to determine if the MRI is sufficient to fully validate an explanted device based upon the characterization of an explanted specimen. An AneuRx device deployed percutaneously 25 months earlier in a 75-year-old patient was removed en bloc at autopsy together with the surrounding aneurysmal sac and segments of the upstream and downstream arteries. Macroscopic pictures were taken and a slice of the cross-section was processed for histology after polymethylmethacrylate (PMMA) embedding. For the magnetic resonance imaging investigation, the device was inserted in a Biospec 4.7 T MRI system with a 20 mm diameter birdcage resonator used for both emission and reception. A Spin-Echo (SE) was used to acquire both T1 proton density (PD) and T2 weighted images. A gradient-echo (GE) sampling of a free induction decay (GESFID) was used to generate multiple GE images using a single excitation pulse so that four images at different TE were obtained in the same acquisition. The selected explanted device was outstandingly well-healed compared to most devices harvested from humans. No inflammatory process was observed in contact or at distance of the materials. In MRI T1 images display no specific contrast and were homogeneous in the different tissues. The contrast was improved on proton density weighed images. On the T2 weighed images, the different areas were well identified. The diffusion images displayed in the surrounding B region had the greatest diffusion coefficient and the greatest anisotropy. The MRI analysis of the explanted AneuRx device illustrates the possibilities of this technique to characterize the interaction of the endovascular graft with the surrounding tissues. MRI is a breakthrough to investigate explanted medical devices but it also can be advantageously used in vivo to obtain virtual biopsies, because real biopsies to determine the 3 Bs (biocompatibility, biofunctionality and bioresilience) cannot be carried out as they could obviously initiate infection and degradation of the foreign materials.

Abstract

We sought to determine whether intermittent short-duration exposure to low wall shear stress could induce intimal thickening in arteries chronically exposed to high shear stress. An arteriovenous fistula (AVF) was created between the left common carotid artery and the corresponding external jugular vein in 20 Japanese white male rabbits. After 4 weeks, blood flow was increased 10-fold to 182 +/- 39 ml/min and shear stress was increased to 33.4 +/- 13 dyn/cm(2). The AVF was then occluded for 1 h by finger compression with an 85% reduction in carotid artery blood flow (27 +/- 7 ml/min) and a reduction in wall shear stress to 4.9 +/- 1.7 dyn/cm(2) (P < 0.0001). Release of finger compression restored flow to the AVF and high shear stress to the carotid artery. This procedure was repeated at weekly intervals with a cumulative total of 4 h of low shear stress exposure. Arteries exposed to intermittent low shear stress developed a layer of intimal thickening which consisted of 3-4 layers of smooth muscle cells lined with thin elastic fibers and medial hyperplasia. Control arteries exposed to 8 weeks of continuous high shear had no intimal thickening. Transient exposure to low shear stress upregulated TGF-beta1, MMP-2, -14, and TIMP-2 gene expression while MMP-9 expression was downregulated. We conclude that repeated, intermittent short-duration exposure to low shear stress in the setting of high flow and high shear stress can induce arterial intimal thickening. Short-duration alterations in hemodynamic forces can induce rapid vascular cell message expression, which may effect arterial remodeling. This experiment suggests that a threshold value of 5 dyn/cm(2) may be needed in order to initiate and sustain the intimal thickening response.

Abstract

Autologous brachiobasilic transposition arteriovenous fistulas (AVFs) are desirable but require long incisions and extensive surgical dissection. To minimize the extent of surgery, we developed a catheter-based technique that requires only keyhole incisions and local anesthesia.The technique involves exposure and division of the basilic vein at the elbow. A guidewire is introduced into the vein, and a 6F "push catheter" is advanced over the guidewire and attached to the vein with sutures. Gently pushing the catheter proximally inverts, or intussuscepts, the vein. Side branches that are felt as resistances when pushing the catheter forward are localized, clipped, and divided under direct vision. Throughout the procedure, the endothelium always remains intraluminal. The basilic vein is externalized at the axilla without dividing it proximally and is tunneled subcutaneously, where it is anastomosed to the brachial artery.Thirty-two patients underwent the procedure--31 as outpatients. The mean duration of operation was less than 90 minutes. All patients tolerated the procedure well, and 31 required only intravenous sedation and local anesthesia. At a mean follow-up of 8 months, the primary patency rate of AVFs in patients with basilic vein diameters of 4 mm or more on preoperative duplex ultrasonography was 80%, vs 50% for those with vein diameters less than 4 mm. Overall, 78% of patent AVFs were being successfully accessed and 22% were still maturing at last follow-up.Autologous brachiobasilic transposition AVFs can be created by using catheter-mediated techniques that facilitate the mobilization and tunneling of the basilic vein through small incisions. Medium-term data suggest that the inversion method results in acceptable maturation and functionality of AVFs created with this technique.

Abstract

Delayed endograft metallic strut failures detected in vivo with multidetector row computed tomography (MDCT) are reported in two patients who underwent endovascular abdominal aortic aneurysm repair with AneuRx and Talent endografts. In both instances, nitinol fractures were associated with proximal migration and type I endoleak. In both cases, the metallic strut fractures were detected with transverse sections from 16-channel MDCT angiograms and confirmed by using volume rendering. These cases highlight the previously unreported ability of thin-section, high-resolution MDCT angiography to detect endograft strut fractures.

Abstract

Angioplasty and stenting of short segment obstructions is highly effective in the treatment of aorto-iliac occlusive disease. However, long-segment, diffuse and calcific aorto-iliac atherosclerosis is most effectively treated with surgical bypass. While aorto-femoral bypass procedures are durable and effective, too often patients are elderly, high risk and poor candidates for open surgery. Endografting of the abdominal aorta and iliac arteries is aimed at improving the short and long-term results of endovascular treatment of extensive, end-stage aorto-iliac disease. Aorto-iliac endografts are widely used in the treatment of aneurysmal disease. Early experiences with endografts in the treatment of occlusive disease are promising. However, evidence that long-term patency of endografts will be substantially better than angioplasty and stenting is not yet available. Prospective clinical trials are needed to determine the role of endografts in the treatment strategy of aorto-iliac occlusive disease.

Abstract

Current clinical trials evaluating carotid stenting have focused on high-risk patients and may not reflect the broad population of patients with carotid stenosis who undergo treatment to prevent stroke. The Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS) phase I study is a multicenter, prospective, nonrandomized trial designed to address the question of whether carotid stenting (CAS) with cerebral protection is comparable to carotid endarterectomy (CEA) in patients with symptomatic and asymptomatic carotid stenosis.Patients with symptomatic (with >50% stenosis) or asymptomatic (with >75% stenosis) carotid stenosis were entered into the study in a 2:1 ratio of carotid stent and GuardWire Plus distal protection device. This unique trial model was developed through collaboration with the International Society of Endovascular Specialists, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, the National Institutes of Health, and industry representatives. The primary end points included death and stroke at 30 days and a composite 1-year end point of death, stroke, or myocardial infarction (MI) from 0 to 30 days and death or stroke from 31 days to 1 year. The secondary end points included residual stenosis, restenosis, repeat angiography, and carotid revascularization at 30 days and 1 year and quality-of-life changes at 1 year.A total of 397 patients (254 CEA and 143 CAS) were enrolled in the study: 32% were symptomatic and 68% were asymptomatic. There were no significant differences in patient characteristics, symptoms, or surgical risk profiles between groups at baseline. Kaplan-Meier analysis revealed no significant differences in combined death/stroke rates at 30 days (3.6% CEA vs 2.1% CAS) or at 1 year (13.6% CEA vs 10.0% CAS). Similarly, there was no significant difference in the combined end point of death, stroke, or MI at 30 days (4.4% CEA vs 2.1% CAS) or at 1 year (14.3% CEA vs 10.9% CAS). There were no significant differences between CEA and CAS in the secondary end points of residual stenosis (0% CEA vs 0.9% CAS), restenosis (3.6% CEA vs 6.3% CAS), repeat angiography (2.1% CEA vs 3.6% CAS), carotid revascularization (1.0% CEA vs 1.8% CAS), or change in quality of life (-1.56 points CEA vs -4.22 points CAS).The CaRESS phase I study suggests that the 30-day and 1-year risk of death, stroke, or MI with CAS is equivalent to that with CEA in symptomatic and asymptomatic patients with carotid stenosis.

Abstract

To determine the long-term outcome after endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms (AAA).Review the primary outcome measures of patients treated with endovascular grafts (EG) in the Lifeline Registry of EVAR. The registry contains data on 2,664 EG patients and 334 open surgical control (SC) patients collected under four multicenter Investigational Device Exemption (IDE) clinical trials that lead to United States Food and Drug Administration (FDA) approval with mandatory 5-year follow-up. Primary outcome measures include operative mortality, AAA-related death, all-cause mortality, aneurysm rupture, and surgical conversion.Pooled data from IDE clinical trials revealed that EG patients were 3 years older (73 +/- 8 years) than SC patients (70 +/- 8 years, P < .01) and had significantly more cardiac comorbidities before treatment. However, there was no difference in 30-day operative mortality between EG (1.7%) and SC (1.4%) (P = .72). Both EG and SC were successful in preventing rupture, with freedom from aneurysm rupture in 99.8% of EG and 100% of SC patients at 1 year (P = .51). Freedom from rupture remained at 99% in years 1 to 6 after EG, with no increasing risk of late rupture. There was no significant difference in the AAA-related death rate at 1 year between EG (98.2%) and SC (98.6%) (P = .64). Freedom from AAA-related death remained at 98% in years 1 to 6 after EG, with no increasing risk of late AAA-related death. Kaplan-Meier analysis at 6 years revealed freedom from aneurysm rupture in 99%, freedom from AAA-related death in 98%, and freedom from surgical conversion in 95% of EG patients. There was no difference in survival at 4 years between EG (74%) and SC (71%) (P = .49). Overall EG patient survival at 5 years was 66% and at 6 years was 52%. Women had a higher risk of rupture (2.4%) than men (1.2%) (P = .01) and a higher rate of surgical conversion (8.3%) than men (3.8%) (P < .01) but had the same low AAA-related death rate (3.5%) as men (2.1%) (P = .16) at 5 years. Most secondary interventional procedures (85%) were performed < or =30 days after EVAR. Freedom from secondary intervention was 84% at 1 year and 78% at 5 years.Endovascular aneurysm repair using FDA-approved devices is a safe, effective, and durable treatment for anatomically suited patients with infrarenal abdominal aortic aneurysms.

Abstract

To report successful endovascular repair of thoracic aortic aneurysms in 2 patients with human immunodeficiency virus (HIV).Thoracic and abdominal aortic aneurysms (AAA) were found in a 60-year-old woman 1 year after she was diagnosed with HIV. Because of pain and risk of rupture, the AAA was repaired with conventional open techniques in February 1997, while the thoracic aneurysm was excluded in a staged procedure using a homemade endograft delivered through a 10-mm conduit sewn to the aortic tube graft. Two months later, new aneurysms were found in the superficial femoral arteries bilaterally; both were excised and replaced with vein grafts. After 7 years, the patient is well and no longer takes antiretroviral medication. Surveillance imaging shows continued patency of the stent-graft without evidence of leak or migration. In a more contemporary case, a 46-year-old man was found to have 5 focal aneurysms in the aorta; the most proximal descending thoracic aneurysm increased 2 cm in 2 weeks. The two thoracic aneurysms were successfully excluded using 2 Excluder stent-grafts. At 7 months, he was doing well, and the aneurysm had shrunk 11 mm.Endovascular and open treatment of HIV-related aneurysms is possible, with excellent long-term results. Patients with long-life expectancy should be treated according to the same guidelines as patients without HIV.

Abstract

To examine the feasibility and clinical outcome of a novel, minimally invasive technique for harvesting the great saphenous vein (GSV) for use in peripheral arterial bypass surgery.Between May 2001 through March 2003, 27 patients (15 men; mean age 71+/-10 years) underwent extremity bypass procedures for limb salvage (88%) or disabling claudication (12%) using the inversion technique to harvest the GSV. The veins were turned "inside out" using a unique catheter and guidewire system. With the endothelial surface exposed, valve leaflets were excised, and adherent thrombus was washed away. Veins were inverted again to turn the endothelial surface back inside the lumen for use as a bypass conduit.Inversion vein harvesting and arterial bypass were completed in 24 (89%) of 27 patients; 2 patients were treated with synthetic grafts because of small GSVs. Another patient was found after vein harvesting to have inadequate arterial outflow despite a good quality conduit. The average vein length was 45+/-10 cm; a mean 4+/-1 incisions were made, including those for arterial exposure. Incisions made to divide vein tributaries averaged 2 cm in length. Duration of vein harvesting was 25 minutes (range 5-80). Wound complications were minor (2 hematomas, 2 cases of erythema, 2 seromas). Of 6 grafts that occluded after 30 days, 5 involved small-diameter vein grafts (< 3.5 mm). At a mean 12 months, primary and assisted primary graft patency rates were 88% (14/16) and 94% (15/ 16), respectively, for grafts with minimum diameters > or = 4 mm versus 38% (3/8) primary patency for veins < 4 mm (n = 8, p < 0.001). The limb salvage rate was 92% (22/24).Over-the-wire inversion saphenectomy is a simple and reliable minimally invasive technique for arterial bypass. Incisions are small and cosmetically superior to those of the traditional long incision method. One-year follow-up suggests that grafts harvested by inversion technique have excellent durability when the minimum vein diameter is > or = 4 mm, as determined by preoperative vein mapping.

Abstract

To determine the impact on late postoperative renal function of suprarenal and infrarenal fixation of endografts used to treat infrarenal abdominal aortic aneurysm (AAA).Retrospective analysis of 277 patients treated from 2000 to 2003 with three different endografts at two clinical centers. Five patients on dialysis for preoperative chronic renal failure were excluded. Group IF of 135 patients treated with an infrarenal device (Medtronic AneuRx) was compared with group SF of 137 patients treated with a suprarenal device (106 Cook Zenith and 31 Medtronic Talent). Renal function was evaluated by calculating preoperative and latest postoperative creatinine clearance (CrCl) using the Cockcroft formula. Patients who developed a >20% decrease in CrCl were considered to have significantly impaired renal function.There were no significant differences in patient age, sex, aneurysm size, preoperative risk factors, dose of intra- and postoperative contrast, or baseline CrCl (IF: 69.3 mL/min, SF: 71.7 mL/min, P = .4). Follow-up time of 12.2 months was the same in both groups. CrCl decreased significantly during the follow-up period in both groups (IF: 69.3 mL/min to 61.7 mL/min, P < .01; SF: 71.7 mL/min to 64.9 mL/min, P < .03). Postoperative CrCl (IF: 61.7 mL/min, SF: 64.9 mL/min, P = .3), and the rate of CrCl decrease during the follow-up period (IF: -10.9%, SF: -9.5%, P = .2) was not different between the two groups. The number of patients with a >20% decrease in CrCl was not different between the two groups (IF: n = 35 [25.9%], SF: n = 41 [29.9%], P = .46). However, the magnitude of decrease in CrCl in patients with renal impairment was greater in patients treated with suprarenal fixation endografts (SF: -39%) compared with those treated with infrarenal endografts (IF: -31%, P = .005). This greater degree of renal impairment was not due to identifiable differences in preoperative risk factors, age, or baseline CrCl. No patients in these series required dialysis.Regardless the type of endograft used, there is a 10% decrease in CrCl in the first year after endovascular aneurysm repair. Suprarenal fixation does not seem to increase the likelihood of postoperative renal impairment. Decline in renal function over time after endovascular aortic repair is probably due to multiple factors, and measures known to be effective in protecting kidneys should be considered for these patients. Long-term follow-up with measurement of CrCl, along with renal imaging and regular blood pressure measurements, should be performed to detect possible late renal dysfunction. Prospective studies comparing suprarenal versus infrarenal fixation are needed to confirm those results.

Abstract

To evaluate displacement and bending of the renal arteries during respiration.Seven men (mean age 59+/-7 years, range 54-71) were imaged with contrast-enhanced magnetic resonance angiography (MRA). Two phases of the MRA were acquired during separate normal inspiration and expiration breath-holds. Displacement of the kidneys and renal ostia and changes in renal branch angle were measured in both coronal and axial views. Arterial curvature and distances between inspiration and expiration renal artery centerlines were computed at 1-mm intervals for the first 2 cm of each branch.Significant kidney displacement was observed in both the coronal and axial views, with maximum displacement on the right side; the right kidney at expiration was 13.2+/-7 mm superior and 6.3+/-3.4 mm posterior of its position during inspiration. By comparison, the renal ostia were relatively fixed, displacing 10-fold less than the kidneys. This displacement differential resulted in significant renal branch angle changes between inspiration and expiration, with the branches being more perpendicular at expiration. Right and left branch angles were significantly different from each other in the axial view, with the right artery taking off more anteriorly. The renal artery centerlines were displaced approximately 2.5 mm at a distance of 1 cm from the ostia, with little displacement change in the second centimeter. The right renal artery was more curved than the left, with more respiratory-induced curvature change near the ostia.Positional change of the kidneys during respiration induces both bending and change in angulation of the renal arteries. This bending can have a complex 3-dimensional shape near the ostia. In the setting of renal artery stenting, this motion may adversely affect the artery and/or the stent, possibly contributing to restenosis.

Abstract

To compare the outcome of patients with small abdominal aortic aneurysms (AAA) treated in a prospective trial of endovascular aneurysm repair (EVAR) to patients randomized to the surveillance arm of the UK Small Aneurysm Trial.All patients with small AAA (< or = 5.5 cm diameter) treated with a stent graft (EVARsmall) in the multicenter AneuRx clinical trial from 1997 to 1999 were reviewed with follow up through 2003. A subgroup of patients (EVARmatch) who met the age (60-76 years) and aneurysm size (4.0-5.5 cm diameter) inclusion criteria of the UK Small Aneurysm Trial were compared to the published results of the surveillance patient cohort (UKsurveil) of the UK Small Aneurysm Trial (NEJM 346:1445, 2002). Endpoints of comparison were aneurysm rupture, fatal aneurysm rupture, operative mortality, aneurysm related death and overall mortality. The total patient years of follow-up for EVAR patients was 1369 years and for UK patients was 3048 years. Statistical comparisons of EVARmatch and UKsurveil patients were made for rates per 100 patient years of follow up (/100 years) to adjust for differences in follow-up time.The EVARsmall group of 478 patients comprised 40% of the total number of patients treated during the course of the AneuRx clinical trial. The EVARmatch group of 312 patients excluded 151 patients for age < 60 or > 76 years and 15 patients for AAA diameter < 4 cm. With the exception of age, there were no significant differences between EVARsmall and EVARmatch in pre-operative factors or post-operative outcomes. In comparison to the UKsurveil group of 527 patients, the EVARmatch group was slightly older (70 +/- 4 vs. 69 +/- 4 years, p = 0.009), had larger aneurysms (5.0 +/- 0.3 vs. 4.6 +/- 0.4 cm, p < 0.001), fewer women (7 vs. 18%, p < 0.001), and had a higher prevalence of diabetes and hypertension and a lower prevalence of smoking at baseline. Ruptures occurred in 1.6% of EVARmatch patients and 5.1% of UKsurveil patients; this difference was not significant when adjusted for the difference in length of follow up. Fatal aneurysm rupture rate, adjusted for follow up time, was four times higher in UKsurveil (0.8/100 patient years) than in EVARmatch (0.2/100 patient years, p < 0.001); this difference remained significant when adjusted for difference in gender mix. Elective operative mortality rate was significantly lower in EVARmatch (1.9%) than in UKsurveil (5.9%, p < 0.01). Aneurysm-related death rate was two times higher in UKsurveil (1.6/100 patient years) than in EVARmatch (0.8/100 patient years, p = 0.03). All-cause mortality rate was significantly higher in UKsurveil (8.3/100 patient years) than in EVARmatch (6.4/100 patient years, p = 0.02).It appears that endovascular repair of small abdominal aortic aneurysms (4.0-5.5 cm) significantly reduces the risk of fatal aneurysm rupture and aneurysm-related death and improves overall patient survival compared to an ultrasound surveillance strategy with selective open surgical repair.

Abstract

To report stent-graft repair of a traumatic aortic pseudoaneurysm in proximity to a celiacomesenteric trunk.An 18-year-old woman suffered a large gunshot wound to the right flank. At laparotomy, only a large, nonexpanding right retroperitoneal hematoma was found, which was thought to represent significant penetrating trauma to the kidney mass. The patient was monitored in the intensive care unit. One week later, computed tomography revealed a partially infarcted right kidney and a 2.3-cm supraceliac aortic pseudoaneurysm, with adjacent bullet fragments. An angiogram confirmed the pseudoaneurysm and showed it to be 7 mm from the celiacomesenteric trunk. Endovascular repair was undertaken with a 16 x 55-mm AneuRx stent-graft, which was successfully placed across the aortic pseudoaneurysm without covering the celiacomesenteric trunk. Imaging at 12 months revealed no endoleak and full pseudoaneurysm exclusion.This operative approach is appropriate for the individual patient who has suitable anatomy and a clinical course that requires immediate repair of an aortic injury to prevent further complications and delays in ancillary treatments.

Abstract

The past decade has seen the evolution of an exciting technology that has changed forever the treatment of aortic aneurysmal disease. From rather crude homemade stent-grafts constructed in the surgical suite to elegant commercially manufactured devices in a variety of configurations and sizes, the aortic endograft has experienced a meteoric rise in popularity to become a beneficial, minimally invasive therapy that can obviate the risk of rupture and death. There are now 3 approved endovascular devices on the market for infrarenal abdominal aortic aneurysm repair, and it is likely that additional and improved devices will become available in the future. This review revisits the developmental history of the aortic endograft, noting the ongoing refinements that have arisen from our experiences with the growing population of stent-graft patients. Although research continues to search for solutions to the problems of endoleak and migration, long-term results even with the earlier second and third-generation devices are better than has been achieved with open surgical repair.

Abstract

The primary objective of the CaRESS Phase I trial is to determine the sample size needed to reliably test the hypothesis that carotid stenting systems with distal embolic protection (CAS) is equivalent to carotid endarterectomy (CEA) in the treatment of symptomatic and asymptomatic carotid artery disease in a broad-risk population. A total of 397 patients were treated at 14 clinical centers. The primary endpoint results of combined all-cause mortality and stroke at 30-days and 1-year are presented. The CaRESS Phase I study was able to closely resemble clinical practice and results suggest equivalence between treatment groups.

What is the significance of endoleaks and endotensionSURGICAL CLINICS OF NORTH AMERICAHeikkinen, M. A., Arko, F. R., Zarins, C. K.2004; 84 (5): 1337-?

Abstract

Endovascular repair has been used over a decade as a treatment of abdominal aortic aneurysm, and has become a widely accepted treatment method with a low rate of perioperative complications. Endoleak, perigraft blood flow outside endograft but within aneurysmsac, has been intensively studied during the last 10 years of endovascular aneurysm repair (EVR). The natural history of aneurysms with endoleak and the true clinical significance of various types of endoleaks remains unclear. Type I/III endoleak has been found to be associated with aneurysm rupture, while the risk of rupture of aneurysms with type II endoleak and endotension appears very small. In endotension, the aneurysm sac remains pressurized, even if there is no evidence of an endoleak. Currently,it is accepted that type I/III endoleaks should be corrected, preferably by endovascular means, due to the risk of rupture. If endovascular repair is not possible, then open conversion should be considered. The risk of conversion should be weighed against the risk of aneurysm rupture. Treatment of type II endoleaks and endotension is more controversial. In those with aneurysm enlargement,secondary interventions are often performed.

Abstract

The primary objective of aneurysm repair is to prevent aneurysm rupture while avoiding aneurysm-related death. This manuscript reviews the primary and secondary outcome measures following endovascular aneurysm repair (EVAR) in relation to similar outcome measures for open surgical repair. Both EVAR and open repair are effective in preventing aneurysm rupture, although late ruptures can occur with either treatment method. The late risk of rupture following EVAR is less that 1% per year using current endovascular devices. Aneurysm-related death rate appears to be lower following EVAR compared to open surgery, primarily due to a lower perioperative mortality rate. Actuarial 5-year survival after both endovascular and open aneurysm repair is approximately 70%. Perioperative outcome measures favor EVAR over open repair for patients with suitable anatomy with reduced morbidity and more rapid patient recovery. Short and long-term outcomes following endovascular repair compare favorably to open repair. However, prospective studies are needed to better define the long-term outcomes using comparable endpoints.

Abstract

Artery wall motion and strain play important roles in vascular remodeling and may be important in the pathogenesis of vascular disease. In vivo observations of circumferentially nonuniform wall motion in the human aorta suggest that nonuniform strain may contribute to the localization of vascular pathology. A velocity-based method to investigate circumferential strain variations was previously developed and validated in vitro; the current study was undertaken to determine whether accurate displacement and strain fields can be calculated from velocity data acquired in vivo. Wall velocities in the porcine thoracic aorta were quantified with PC-MRI and an implanted coil and were then time-integrated to compute wall displacement trajectories and cyclic strain. Displacement trajectories were consistent with observed aortic wall motion and with the displacements of markers in the aortic wall. The mean difference between velocity-based and marker-based trajectory points was 0.1 mm, relative to an average pixel size of 0.4 mm. Propagation of error analyses based on the precision of the computed displacements were used to demonstrate that 10% strain results in a standard deviation of 3.6%. This study demonstrates that it is feasible to accurately quantify strain from low wall velocities in vivo and that the porcine thoracic aorta does not deform uniformly.

Abstract

We reviewed the structural findings of explanted AneuRx stent grafts used to treat abdominal aortic aneurysms, and relate the findings to clinical outcome measures.We reviewed data for all bifurcated AneuRx stent grafts explanted at surgery or autopsy and returned to the manufacturer from the US clinical trial and worldwide experience of more than 33,000 implants from 1996 to 2003. Devices implanted for more than 1 month with structural analysis are included in this article. Explant results were analyzed in relation to cause of explantation and pre-explant evidence of endoleak, enlargement, or device migration.One hundred twenty explanted stent grafts, including 37 from the US clinical trial, were analyzed. Mean implant duration was 22 +/- 13 months (range, 1-61 months). Structural abnormalities included stent fatigue fractures, fabric abrasion holes, and suture breaks. The mean number of nitinol stent strut fractures per explanted device was 3 +/- 4, which represents less than 0.2% of the total number of stent struts in each device. The mean number of fabric holes per explanted device was 2 +/- 3, with a median hole size of 0.5 mm(2). Suture breaks were seen in most explanted devices, but composed less than 1.5% of the total number of sutures per device. "For cause" explants (n = 104) had a 10-month longer implant duration (P =.007) compared with "incidental" explants (n = 16). "For cause" explants had more fractures (3 +/- 5; P =.005) and fabric holes (2 +/- 3; P =.008) per device compared with "incidental" explants, but these differences were not significant (P =.3) when adjusted for duration of device implantation. Among clinical trial explants the number of fabric holes in grafts in patients with endoleak (2 +/- 3 per device) was no different from those without endoleak (3 +/- 4 per device; P = NS). The number of fatigue fractures or fabric holes was no different in grafts in clinical trial patients with pre-explant aneurysm enlargement compared with those without enlargement. Pre-explant stent-graft migration was associated with a greater number of stent strut fractures (5 +/- 7 per device; P =.04) and fabric holes (3 +/- 3 per bifurcation; P =.03) compared with explants without migration. Serial imaging studies revealed inadequate proximal, distal, or junctional device fixation as the probable cause of rupture or need for conversion to open surgery in 86% of "for cause" explants. Structural device abnormalities were usually remote from fixation sites, and no causal relationship between device findings and clinical outcome could be established.Nitinol stent fatigue fractures, fabric holes, and suture breaks found in explanted AneuRx stent grafts do not appear to be related to clinical outcome measures. Longer term studies are needed to confirm these observations.

Abstract

To present the management of acute arterial ischemia following major abdominal and orthopedic surgery using a percutaneous thrombectomy device and a low dose of thrombolytic agent.A 38-year-old woman with T-8 paraplegia from a traumatic fall developed pelvic osteomyelitis, for which a left hemipelvectomy, hysterectomy, and partial vaginal resection were performed. Twelve hours after the procedure, the patient developed an ischemic left leg. Computed tomographic angiography demonstrated an occlusion of the left external iliac and common femoral arteries. A Turbo Trellis percutaneous thrombectomy device was used to lyse the left external iliac artery thrombosis using 1 mg of tissue plasminogen activator infused between the proximal and distal occluding balloons of the device. Total dispersion time was 5 minutes. There was complete thrombus removal without any significant bleeding complications. At 6 months, the artery remains widely patent.Combination therapy with mechanical thrombectomy devices and low dose thrombolytic agents can be used to treat acute arterial occlusions at a single setting. The increased speed of the Turbo Trellis may allow for smaller doses of thrombolytic agents and shorter treatment times.

Abstract

Late complications following endovascular aneurysm repair indicate the need for long-term surveillance. Clinical trials involving endoluminal stent grafts have typically used computed tomography angiography as the main imaging modality for surveillance. However, computed tomography angiography exposes the patient to higher levels of ionizing radiation, nephrotoxic agents, and increased cost compared to duplex ultrasound. Duplex ultrasound scanning has been widely used for surveillance of abdominal aortic aneurysms for many years. It is well established and the procedure of choice for noninvasive imaging of the aorta. It offers the advantages of easy access, decreased cost, no radiation exposure, and no nephrotoxicity. There is little controversy about duplex scanning for preoperative patient evaluation or surveillance of patients with small aneurysms. However, the use and reliability of duplex scanning in the evaluation and surveillance of patients following endovascular repair is controversial. This article will discuss the benefits, techniques, and limitation of duplex ultrasound in the long-term surveillance of endografts following endovascular abdominal aortic aneurysm repair.

A new approach to carotid angioplasty and stenting with transcervical occlusion and protective shunting: Why it may be a better carotid artery intervention18th Annual Meeting of the Western-Vascular-SocietyChang, D. W., Schubart, P. J., Veith, F. J., Zarins, C. K.MOSBY-ELSEVIER.2004: 994–1001

Abstract

The purpose of this study was to evaluate the effectiveness and demonstrate the advantages of a new technique for carotid angioplasty and stenting (CAS) with proximal cerebral protection through a direct transcervical approach, as compared with a percutaneous transfemoral approach.CAS procedures were carried out in 25 consecutive patients, 4 with the femoral approach and 21 through a 2-cm incision at the base of the neck, with the patient under local anesthesia. For transcervical occlusion and protective shunting (TOPS), a short 9F sheath was inserted directly into the common carotid artery and connected to a 6F sheath placed percutaneously in the ipsilateral internal jugular vein. After clamping the common carotid artery proximal to the 9F sheath, internal carotid artery blood flow reversal was confirmed or an occluding external carotid balloon was placed. A filter interposed between the arterial and venous sheaths collected embolic debris from transcarotid manipulations. The arterial puncture was directly repaired with suture. Neurologic status was assessed with the National Institutes of Health stroke scale by an independent neurology consultant before and after the procedure.One of the four percutaneous femoral approaches that failed because of tortuous anatomy was successfully treated with TOPS. Angiographic confirmation demonstrating resolution of asymptomatic (>80%; n = 12) stenosis or symptomatic (>60%; n = 12) stenosis was achieved in all patients with stents. A 0% technical failure rate and 0% combined 30-day stroke or mortality rate were achieved in all CAS attempted with TOPS. There were no hematomas in the cervical group, despite pretreatment with clopidogrel bisulfate and heparin, and one hematoma in the femoral group after failure of a Perclose arterial closure device. In one of the patients in the femoral group bilateral cholesterol emboli to the toes developed.TOPS solves problems of access, embolization into the cerebral and peripheral circulation, and specialized cerebral protection devices, and enables secure closure of the access vessel in patients given anticoagulation therapy. TOPS may provide a safer, more effective, economical means for performing CAS.

Abstract

We investigated the effects of sequential and prolonged exposure to high and low wall shear stress on arterial remodeling using a rabbit arteriovenous fistula (AVF) model. Blood flow was increased by approximately 17-fold to 20-fold when the AVF was open, and returned to normal when the AVF was occluded. Repeated opening and closing of the AVF resulted in sequential exposure of the artery to high and low wall shear stress. High flow and high wall shear stress induced arterial dilatation, elongation, and tortuosity, without intimal thickening. The common carotid artery was elongated 37% after 4 weeks of high flow, and was shortened 10% after 6 weeks of normal flow. Subsequent cycles of high flow induced less elongation, with less shortening after return to normal flow. Enlargement of the distal segment was more dramatic than in the proximal segment, despite exposure to the same volume of flow and the same initial high wall shear stress after creation of the AVF. The distal carotid segment enlarged more than did the proximal segment during each exposure to high flow. In segments of carotid artery exposed to low wall shear stress (<5 dynes/cm(2)) intimal thickening developed. These changes were maximal in the distal carotid segment, just before the AVF. Each cycle of low wall shear stress induced intimal thickening accompanied by medial hyperplasia. Intimal thickening was inhibited during periods of high flow when wall shear stress was high. Three cycles of flow alteration induced three layers of intimal thickening in the distal arterial segment, two layers of intimal thickening in the middle segment, and one layer of intimal thickening in the proximal segment. Long-term exposure to low wall shear stress induced severe intimal thickening and medial hyperplasia in different segments. Thus the response of the carotid artery afferent to an AVF varies along the length of the artery, with maximum enlargement, elongation, and tortuosity in the distal segment, just proximal to the AVF. Similarly, intimal thickening in response to low wall shear stress is maximal in the distal carotid artery. It appears that intimal thickening is related to local levels of low wall shear stress, and occurs when wall shear stress chronically falls to less than 5 dynes/cm(2).

Abstract

This preliminary study examined the technical efficacy, safety, and cost of treating arterial occlusions with a single device that combines pharmacologic and mechanical thrombolysis.The technical success, bleeding complications, and costs for the first 26 consecutive patients in whom lower extremity ischemia was treated with the Trellis infusion catheter (TIC) were analyzed. Procedure time, thrombolytic infusion time, technical success, bleeding complications (major and intracranial hemorrhage), interventional suite time, and 30-day amputation-free survival were evaluated.15 of 26 patients (58%) who received treatment with the TIC had acute arterial occlusions, and 11 of 26 patients (42%) had nonacute arterial occlusions. Nineteen of 26 patients (73.1%) received treatment of an infrainguinal occlusion, and 7 of 26 patients (26.9%) received treatment of a suprainguinal occlusion. Lower extremity native arteries were treated in 18 of 26 patients (69%), and lower extremity bypass grafts in 8 of 26 patients (31%). The technical success rate with TIC treatment was 92%, and the 30-day amputation-free survival rate was 96%. There was no difference in technical success or amputation-free survival rate between acute versus nonacute arterial occlusions, native artery versus bypass grafts, and suprainguinal versus infrainguinal arterial occlusions. Procedure time was 2.1 +/- 0.9 hours, and infusion time was 0.3 +/- 0.2 hours. There were no bleeding complications; however, 3 of 26 patients (11.5%) required further intervention to treat distal embolization. The overall mean cost for patients with TIC treatment was $3216 +/- $1740.Early results of TIC treatment in patients with arterial occlusions suggest that it is as effective as traditional catheter-directed thrombolysis. Furthermore, there were no bleeding complications, likely the result of TIC requiring shorter procedure and infusion times.

Abstract

To determine how many patients with abdominal aortic aneurysms (AAA) meet the anatomical selection criteria for AneuRx stent-graft repair in community hospitals of Northern California.The records were reviewed of 220 AAA patients (171 men, 49 women) who were considered for endovascular repair by the treating vascular surgeon at 28 community hospitals in Northern California between January and October 2001. Contrast computed tomographic angiography (CTA) and selective arteriography were performed at each institution and reviewed by a centralized, independent image-reading center. Selection criteria determined by the manufacturer and published in the indications for use were applied to each set of imaging studies. The number of patients who met inclusion criteria were recorded, as were the anatomical characteristics of each aneurysm.The mean aneurysm size in the 220 patients was 55.3 +/- 0.7 mm. Among these patients, 122 (55%) were judged to be candidates for endovascular repair and 98 (45%) were considered ineligible. The primary anatomical reason for ineligibility was a short infrarenal neck in 43 (44%) patients, followed by a large proximal neck diameter (25, 25%), iliac aneurysms (10, 10%), extremely tortuous or calcified neck (7, 7%), iliac occlusion (6, 6%), and small distal aortic bifurcation and accessory renal arteries (5, 5%). Four (4%) patients were classified as non-candidates due to poor quality imaging. There was no difference in aneurysm diameter (54.0 +/- 0.8 versus 57.1 +/- 1.2 mm, p=NS) or age (72.2 +/- 1.2 versus 74.6 +/- 2.2 years, p=NS) between candidates and non-candidates. However, proportionally more men (60%) than women (39%) were eligible for endovascular repair with the AneuRx stent-graft (p<0.05). All 122 patients who were considered candidates for endovascular repair were treated, with successful stent-graft placement achieved in 121 (99%).Fifty-five percent of patients considered for endovascular AAA repair in community hospitals in Northern California met the anatomical selection criteria for the AneuRx stent-graft. Men appeared to be twice as likely to meet the eligibility requirements as women. Unfavorable infrarenal neck anatomy was the primary exclusion criterion for endovascular repair in this community setting.

Abstract

The purpose of this study was to determine the incidence and significance of aneurysm enlargement, with or without treatment, in relation to the primary end points of rupture, surgical conversion, aneurysm-related death, and survival following endovascular repair.Aneurysm (AAA) size changes and clinical outcome of all patients treated from 1997 through 1998 during the Phase II AneuRx multicenter clinical trial of endovascular AAA repair were reviewed. Aneurysm dimensions and the presence or absence of endoleak were determined by an independent core laboratory, with enlargement or shrinkage defined as a diameter change of 5 mm or more compared with baseline.Among 383 patients (89% men, 11% women, age 73 +/- 9 years), with a mean device implant time of 36 +/- 11 months (median = 39 months), aneurysm diameter decreased from 5.7 +/- 1.0 at baseline to 5.2 +/- 1.0 at 3 years (P =.0001). A total of 46 patients (12%) experienced AAA enlargement, 199 patients (52%) had no change in AAA diameter, and 138 patients (36%) had a decrease in AAA diameter of 5 mm or more. Significant risk factors for enlargement included age (enlargement patients were 4 years older on average than patients with aneurysms that decreased in size; P =.002) and the presence of an endoleak (P

Abstract

We reviewed the incidence of stent-graft migration after endovascular aneurysm repair in a prospective multicenter trial and identified factors that may predispose to such migration.All patients who received treatment during the course of the multicenter AneuRx clinical trial were reviewed for evidence of stent-graft migration over 5 years, from 1996 to 2001. Post-deployment distance from the renal arteries to the proximal end of the stent graft and the proximal fixation length (length of the infrarenal neck covered by the stent graft) were determined in patients for whom pre-procedure and post-procedure computed tomography scans were measured in an independent core laboratory.Stent-graft migration was reported in 94 of 1119 patients, with mean time after device implantation of 30 +/- 11 months. Freedom from migration was 98.6% at 1 year, 93.4% at 2 years, and 81.2% at 3 years (Kaplan-Meier method). Subset (n = 387) analysis revealed that initial device deployment was lower in 47 patients with migration, as evidenced by a greater renal artery to stent-graft distance (1.1 +/- 0.7 cm), compared with 340 patients without migration (0.8 +/- 0.6 cm; P =.006) on post-implantation computed tomography scan. Proximal fixation length was shorter in patients with migration (1.6 +/- 1.4 cm) compared with patients without migration (2.3 +/- 1.4 cm; P =.005). There was significant variation in migration rate among clinical sites (P

Abstract

To report successful combined percutaneous mechanical thrombectomy and pharmacological lysis for axillosubclavian vein thrombosis, with rapid clot removal at a single setting using low-dose thrombolysis.Two consecutive patients presented with arm swelling; the diagnosis of axillosubclavian vein thrombosis was confirmed with duplex ultrasound. Both patients were treated percutaneously with the Solera mechanical thrombectomy device, after which 5 mg of tissue plasminogen activator were delivered within approximately 10 minutes via the Trellis infusion catheter to remove any residual thrombus. Completion venography and serial duplex ultrasound scans in follow-up demonstrated widely patent axillosubclavian veins with no residual thrombus in both cases.Standard treatment of axillosubclavian vein thrombosis may require 12 to 36 hours, with multiple trips to the angiography suite. The novel technique combining mechanical thrombectomy and pharmacological lysis can be performed safely and successfully at a single setting with a small dose of the lytic drug.

Abstract

A total of 1193 patients with infrarenal abdominal aortic aneurysms were treated with the AneuRx Stent Graft System at 19 US investigational centers from 1996 to 1999. This report summarizes clinical data collected and analyzed as of August 28, 2002. There have been 10 late (>30 days) aneurysm ruptures, 8 late (>30 days) aneurysm-related deaths, and 38 late (>30 days) surgical conversions, including 8 for rupture. Kaplan-Meier analyses of the primary outcome measures at 4 years indicate the following: a freedom from rupture rate of 98.4%; a freedom from surgical conversion rate of 90.4%; a freedom from aneurysm-related death rate of 96.9%; and a probability of survival rate, based on all-cause mortality, of 62.4%. Secondary outcome measures at 4 years include stent graft patency in 96.4%, endoleak in 13.9%, aneurysm enlargement in 11.5% and stent graft migration in 9.5% of patients. These results provide evidence that the AneuRx Stent Graft System continues to be a safe and effective treatment option for appropriately selected patients with infrarenal abdominal aneurysms.

Abstract

The goals of this laboratory model were to evaluate the performance of the surgical team and endolaparoscopic techniques in the porcine model of infrarenal abdominal aortic repair.Twenty-four pigs underwent full endolaparoscopic aorto-aortic graft implantation with voice-activated computerized robotics. The first group of 10 pigs (acute) was sacrificed while under anesthesia at 0.5 hours (5 animals) and 2 hours (5 animals). The second group of 14 pigs (survival) were recovered from anesthesia and maintained for 7 hours (5 pigs) and 7 days (9 pigs) prior to sacrifice. Survival animals were observed for evidence of hind limb dysfunction. All grafts were visually inspected at autopsy.All animals survived the operation. All grafts were successfully implanted, and all were patent with intact anastomoses at autopsy. Mean aortic clamp time for each group was as follows: acute, 92.9 +/- 28.04 minutes; survival, 59.6 +/- 13.8 minutes; P=0.0008. Total operative time for each group was as follows: acute, 179 +/- 39.6 minutes; survival, 164.6 +/- 48 minutes; P=0.44 ns. Estimated blood loss for each group was as follows: acute, 214 -/+ 437.8 mL; survival 169.2 +/- 271 mL; P=0.76 ns. from respiratory arrest; 1 animal suffered motor sensory dysfunction of the hind limbs (spinal cord ischemia); significant bleeding occurred in 6 of 24 pigs; 8 of the 9 seven-day survivors required minimal pain medication and had normal hind limb function.The reduction in aortic clamp time, total operative time, and blood loss as the study progressed indicate the feasibility of this surgical protocol and the maturation of the learning process, which is paramount in prevention of 2 main sources of morbidity: bleeding and spinal cord ischemia. The reduction in aortic clamp time between the acute and survival groups was dramatic and statistically significant. An intensive formal training program combining dry and live surgical laboratories is deemed essential for the development of endoscopic skill sets necessary for this challenging procedure.

Abstract

To compare early and late functional outcomes, as well as survival and recovery, following endovascular or open repair of abdominal aortic aneurysm (AAA).Between 1996 and 2000, 294 patients underwent AAA repair (141 open and 153 endovascular); 57 patients from each group had 12-month follow-up for functional outcome assessment. Recovery was measured as hospital length of stay, skilled nursing requirement, and hospital readmission within 1 year to determine cumulative hospital utilization. Early (<6 months) functional outcomes were measured by activity level and convalescence days following surgery. Late (>6 months) functional outcomes were measured as ambulation, independent living, and employment status pre- and postoperatively.Operative mortality for open repair was 5 (3.5%) compared to 1 (0.6%) after an endovascular procedure (p<0.05). The endovascular group had a shorter hospital stay (2.8+/-2.8 versus 8.3+/-4.5 days) and fewer skilled nursing requirements (0% versus 26%; p<0.001). Cumulative hospital utilization over 12 months was 3.8 days for endovascular patients and 13.8 days for open repair (p<0.001). Recovery time was 99.3+/-84.1 days (range 14-365) in conventionally treated patients and 32.1+/-43.5 days (range 7-180) in the stent-graft group (p<0.001). At 6 months, 43 (75%) open and 54 (95%) endovascular patients had full recovery (p<0.01). Activity levels decreased in 13 (23%) open and 3 (5%) endovascular patients after surgery (p<0.01). There were no differences in ambulation, independent living, or employment status before and after treatment.Periprocedural survival following aneurysm repair is improved with endovascular grafting compared to open surgery, and recovery is more rapid, with a 78% reduction in total hospital days. Early functional outcomes are markedly improved with endovascular repair, while there is no difference in late functional outcomes between the procedures.

Abstract

Endovascular grafting of abdominal aortic aneurysms should be offered only to those patients with suitable anatomy. This is especially true at the level of the proximal aortic neck in order to secure long-term proximal fixation. Aortoiliac anatomy is easy to understand conceptually, however, it is difficult to define and measure quantitatively. In this article, we discuss the use of three dimensional computed tomographic angiography to determine aneurysm morphology and select patients for endovascular repair. Specifically, we apply our methods to define and measure angulation of the aorta and iliac arteries. The anatomic definition of the angulation of the proximal aortic neck is emphasized.

Abstract

Endothelial cells are stable and quiet in normal animals. They arrange regularly and have a smooth lumen surface and thin endothelial wall. According to Thoma's principle (1893) and Kamiya and Togawa's principle (1980) on the relationship of the vascular diameter to flow alteration, blood flow is in equilibrium to the diameter and in a physiological state. That is to say, there is no fast flow or slow flow. To understand the nature of the endothelial cells, we should investigate endothelial cells under flow alteration to break the equilibrium state. Endothelial cells under increased flow were studied in arteries with an arteriovenous fistula or in the capillaries of myocardium with volume-overloaded hearts or of the skeletal muscle by electrical stimulation. Those under decreased flow were studied by the closure of the fistula or by ceasing the stimulation. Endothelial cells in the coarctation of the arteries were also observed. Endothelial cells were activated by increased flow in the arteries and capillaries, while they were inactivated by decreased flow. Endothelial activation is characterized as lumen protrusions, increase of cytoplasmic organelles, abluminal protrusions, basement membrane degradation, internal elastic lamina degradation in the arteries, and sproutings in the capillaries. These are ultrastructurally comparable to angiogenesis. Endothelial inactivation is characterized by the decrease of endothelial cell number with apoptosis, which is ultrastructurally comparable to angioregression. We assume that endothelial cells respond to increased flow by angiogenesis and to decreased flow by angioregression.

Abstract

To compare systemic complications between standard surgery and endovascular repair of abdominal aortic aneurysms (AAA) for both primary and late secondary procedures.At a single center between July 1993 and May 2000, 297 patients (255 men; mean age 73.4 +/- 8.1 years, range 50-93) were treated with open surgical repair; beginning in 1996, 200 (166 men; mean age 73.6 +/- 8.0 years, range 45-96) patients were treated with the AneuRx stent-graft. In a comparison of the cohorts, which were similar in terms of age, gender, and aneurysm diameter, the main outcomes were early major systemic morbidity following the primary procedure to treat the aneurysm and late (>30 days) organ system morbidity for any secondary procedures.Mean length of follow-up for open patients was 20.1 +/- 17.1 months (range 1-150) compared to 12.4 +/- 9.6 months (range 1-60) after endovascular repair (p<0.05). There were 36 (12.1%) systemic complications after the primary open surgery and 15 (7.5%) after endovascular repair (p=NS). There were 43 (14.5%) combined primary and secondary morbidities in the open surgery group versus 15 (7.5%) for patients undergoing endovascular repair (p<0.01). The need for invasive procedures to treat these primary and secondary systemic complications was 4 times greater in the open group (17, 5.7%) than in endograft patients (3, 1.5%) (p<0.05). After secondary procedures (32 in the open group and 30 in the endovascular patients) for graft-related complications, there were 7 (21.9%) adverse events in the open group versus none (0%) for endograft patients (p<0.01). Hospital lengths of stay following both primary and secondary procedures were lower for the endograft patients (p<0.01 and p<0.001, respectively).Endovascular stent-graft repair compared to open surgery has reduced the early and late morbidity by half. Complications that require invasive or secondary surgical procedures and hospitalization are reduced with endovascular repair.

Abstract

Elevated awake resting heart rate (HR) has been shown to be a major risk factor for cardiovascular disease. Since coronary ischaemic events appear to peak during transition from sleep to awake HR, we sought to determine whether the degree of diurnal HR fluctuation (dHRV) is an independent predictor of coronary and peripheral atherogenesis. In this study, we varied both baseline HR and dHRV using sino-atrial node ablation (SNA) in a primate model of diet-induced atherogenesis and determined the degree of plaque formation relative to both HR parameters.HR was recorded continuously for 6 months by an implantable intraaortic sensor/transmitter in 17 active unrestricted male cynomolgus monkeys. In nine monkeys, SNA was employed to create a wide spectrum of dHRV, and the power amplitude of dHRV was determined for the daily HRV cycle with power spectral analysis. After a 6-month diet induction period, percent coronary and carotid stenosis, intimal thickness and area were quantitated in each animal.Total serum cholesterol and mean HR were no different between high ( n= 10) and low ( n= 7) dHRV groups (866 mg% vs. 740 mg%, P> 0.2 and 130 +/- 22 and 115 +/- 13, P> 0.1, respectively). Percent carotid stenosis was markedly greater in both high HR and dHRV animals ([HR], 54 +/- 19 vs. 35 +/- 10, P< 0.04) and ([dHRV], 54 +/- 17 vs. 32 +/- 10, P< 0.01). Significant increases in all measures of coronary atherogenesis were found in high dHRV animals when compared with those with low dHRV (percent stenosis: 48% +/- 22 vs. 23% +/- 16, P< 0.02), (lesion area: 1.2 +/- 0.8 vs. 0.3 +/- 0.3, P< 0.02), and (intimal thickness: 0.3 +/- 0.1 vs. 0.1 +/- 0.1, P< 0.01), respectively. While there was a trend towards greater coronary atherogenesis in animals with high HR, this did not reach statistical significance.Elevated HR and dHRV are both associated with enhanced experimental atherosclerotic plaque formation. However, a greater degree of carotid and coronary atherogenesis is observed in animals with high dHRV. These findings suggest that elevated dHRV is a stronger predictor for susceptibility to atherogenesis than elevated HR alone. Such a relationship may be attributed to the potential role of dHRV in modulating the frequency of adverse near wall haemodynamic forces, which have been shown to induce atherosclerotic plaques. Lowering of dHRV in humans by exercise or pharmacological agents may have a beneficial role in retarding atherosclerotic plaque induction, progression and complication.

Abstract

The response of endothelial cells to altered flow conditions has been studied extensively. However, the indirect effects of shear stress on medial smooth muscle cells (SMCs) have been less well characterized and a murine model of high shear stress has not been available.The hemodynamic changes that occur in a mouse aorta proximal to an aortocaval fistula (ACF) were characterized by measuring blood flow, aortic diameter, and calculating wall shear stress. This model was next used to evaluate cellular activation by assessing beta-galactosidase expression in fos-lacZ transgenic mice. Aortic specimens were examined by a chemiluminescent beta-galactosidase assay, cross-sectional histology, and Hautchen prep en face histology.Immediately after ACF construction, aortic diameter remained unchanged and wall shear stress increased 2.6-fold (49.57 +/- 5.89 to 134.93 +/- 15.69 dyn/cm(2), P < 0.05). Flow-induced aortic enlargement occurred gradually (0.61 +/- 0.03 to 1.18 +/- 0.05 mm at 21 days, P < 0.5) such that by 21 days after ACF, wall shear stress had returned to baseline (56.97 +/- 8.62 dyn/cm(2), P = ns compared to control). Aortas from fos-lacZ mice demonstrated increased beta-gal activity at 6 h and up to 7 days after ACF (1.81 +/- 0.22 rlu/microg in controls vs 41.41 +/- 16.28 rlu/microg at 6 h and 15.17 +/- 1.1 rlu/microg at 7 days, P < 0.5) On histologic evaluation, there was a significant increase in medial SMC staining that was most prominent in cells near the intima (2 +/- 0.3% positive cells in controls vs 67 +/- 10% at 6 h and 11 +/- 7.6 at 7 days, P < 0.5). Endothelial cells, evaluated by en face methods, did not demonstrate significant amounts of beta-gal positivity at the times studied.These in vivo findings using a new high shear stress model suggest that early and sustained activation of medial SMCs is a critical component of flow-induced enlargement. Further evaluation of these events may provide important insights into the mechanisms of pathologic arterial remodeling.

Abstract

This study investigated the effects of high flow and shear stress on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-2 (TIMP-2) during flow-induced arterial enlargement using a model of arteriovenous fistula (AVF) creation on the carotid artery with the corresponding jugular vein in Japanese white male rabbits. Flow increased 8-fold 7 days after AVF. Endothelial cells (EC) and smooth muscle cells (SMC) proliferated with internal elastic lamina (IEL) degradation in response to high flow and shear stress. Expression of MMP-2 mRNA peaked at 2 days (1700-fold) and maintained high level expression. MMP-9 mRNA gave a 10.8-fold increase within 2 days and decreased later. Their proteins were detected in EC and SMC. Membrane type-1-MMP (MT1-MMP) mRNA increased 121-fold at 3 days and maintained high expression. TGF-beta1 was increased after AVF. Two-peak up-regulation of Egr-1 mRNA was recognized at 1 and 5 days of AVF. These results suggest that high flow and shear stress can mediate EC and SMC to express MMP-2 and MMP-9, which degrade cell basement membranes and IEL to induce arterial enlargement. The disproportional increase in MT1-MMP and TIMP-2 might contribute to MMP-2 activation. Egr-1 and TGF-beta1 might play important roles in this process.

Abstract

In vivo quantification of vessel wall cyclic strain has important applications in physiology and disease research and the design of intravascular devices. We describe a method to calculate vessel wall strain from cine PC-MRI velocity data. Forward-backward time integration is used to calculate displacement fields from the velocities, and cyclic Green-Lagrange strain is computed in segments defined by the displacements. The method was validated using a combination of in vitro cine PC-MRI and marker tracking studies. Phantom experiments demonstrated that wall displacements and strain could be calculated accurately from PC-MRI velocity data, with a mean displacement difference of 0.20 +/- 0.16 mm (pixel size 0.39 mm) and a mean strain difference of 0.01 (strain extent 0.20). A propagation of error analysis defined the relationship between the standard deviations in displacements and strain based on original segment length and strain magnitude. Based on the measured displacement standard deviation, strain standard deviations were calculated to be 0.015 (validation segment length) and 0.045 (typical segment length). To verify the feasibility of using this method in vivo, cyclic strain was calculated in the thoracic aorta of a normal human subject. Results demonstrated nonuniform deformation and circumferential variation in cyclic strain, with a peak average strain of 0.08 +/- 0.11.

Abstract

The purpose of this study was to assess the time course of tropoelastin gene expression in the poststenotic dilatation segment of rabbit aorta with experimental coarctation.Midthoracic aortic coarctation was created in rabbits to produce a PSD. The time points of the study after coarctation were 1, 3, and 7 days and 2, 4, and 8 weeks (n = 3 each). Additional animals (n = 6) were subjected to hypercholesterolemia for analysis of tropoelastin expression in intimal lesions. Northern and Western blot analyses were used to quantitate tropoelastin messenger RNA (mRNA) and protein, and immunohistochemistry was used to analyze tropoelastin distribution.Thoracic aortic coarctation produced a moderate stenosis, which resulted in PSD. mRNA levels in the PSD segment decreased at days 1 and 3, followed by an increase at 2 and 4 weeks (P

Abstract

The purpose of this study was to utilize an objective endpoint analysis of aneurysm treatment, which is based on the primary objective of aneurysm repair, and to apply it to a consecutive series of patients undergoing open and endovascular repair.Aneurysm-related death was defined as any death that occurred within 30 days of primary aneurysm treatment (open or endovascular), within 30 days of a secondary aneurysm or graft-related treatment, or any death related to the aneurysm or graft at any time following treatment. We reviewed 417 consecutive patients undergoing elective infrarenal aortic aneurysm repair: 243 patients with open repair and 174 patients with endovascular repair.There was no difference between the groups (open vs endovascular) with regard to mean age +/- standard deviation (73 +/- 8 years vs 74 +/- 8 years) or aneurysm size (64 +/- 2 mm vs 58 +/- 10 mm) (P = not significant [NS]). The 30-day mortality for the primary procedure after open repair was 3.7% (9/243) and after endovascular repair was 0.6% (1/174, P

Abstract

The purpose of this study was to determine the outcome of endovascular aneurysm repair in a defined geographic region during the first 2 years after Food and Drug Administration approval of a new endovascular device.Clinical results of all attempted endovascular aneurysm repairs from 1999 to 2001 with the AneuRx stent graft in the northern California/Nevada region were reviewed. All cases performed in 23 hospitals by 21 endovascular treatment teams were included on an intent-to-treat basis. Community physician training, proctoring, and assistance in case selection was provided by the manufacturer, with outcome monitored by external physician observers and clinical vascular specialists. Results in 22 community hospitals were compared with concurrent results in the regional university hospital training center and with results from the controlled, multicenter AneuRx clinical trial.Endovascular aneurysm repair was attempted in 257 patients by 20 endovascular teams working in 22 community hospitals. The mean number of cases per team was 13 +/- 2 (range, 1 to 36). Patient age was 74.1 +/- 6.5 years (89% men and 11% women), and 29% of patients were not candidates for open surgical repair because of multiple medical comorbidities. Mean aneurysm diameter was 5.7 +/- 0.8 cm. The endoluminal stent graft was successfully deployed in 254 patients (98.8%). In two patients, iliac access could not be obtained, and in one case, the iliac limb was misdeployed and the patient underwent successful open surgical repair. The surgical conversion rate was two of 257 patients (0.8%). The 30-day mortality rate was 1.2%, with one patient dying of stroke, one of multisystem organ failure, and one of cerebral hemorrhage. No device-related deaths occurred. Secondary procedures were performed in 8% of patients. Primary graft patency rate was 98%, and secondary graft patency rate was 100%. Concurrent university training center experience with 100 patients with similar characteristics and aneurysm size was not statistically different (deployment success rate, 100%; 30-day mortality rate, 0%; surgical conversion rate, 0%; secondary procedure rate, 8%). No aneurysm ruptures and no late surgical conversions have been seen in either the community or university experience, with follow-up periods extending to 2 years.Early results of endovascular aneurysm repair introduced into community practice are favorable. Initial community experience, with clinical support from the manufacturer, does not appear to differ significantly from concurrent results in the university training center or from results reported from the multicenter controlled clinical trial with the same device.

Abstract

Cell proliferation and apoptosis are both involved in arterial wall remodeling. Increase in blood flow induces arterial enlargement. The molecular basis of flow-induced remodeling in large elastic arteries is largely unknown.An aortocaval fistula (ACF) model in rats was used to induce enlargement in the abdominal aorta. Aortic gene expression of transforming growth factors beta (TGF-beta) and apoptosis-related factors was assessed at 1 and 3 days and 1, 2, 4, and 8 weeks. Expression levels were determined using a ribonuclease protection assay and western blotting. Cell proliferation and apoptosis were analyzed using BrdU incorporation and TUNEL techniques.Blood flow increased 5-fold immediately after ACF (P<0.05). Lumen diameter of the aorta was 30% and 75% larger at 2 and 8 weeks respectively than those of controls (P<0.05). mRNA levels of TGF-beta1 and TGF-beta3 increased after ACF, peaked at 3 days (P<0.05) and returned to normal level at 1 week and thereafter. Western blotting showed enhanced expression of TGF-beta1 at 3 days and TGF-beta3 at 1 and 3 days and 1 week (P<0.05). mRNA levels of Bcl-xS initially decreased at 1 day, 3 days and 1 week, followed a return to baseline level at 2 weeks. Cell proliferation was observed at all time points after ACF (P<0.001 vs. controls) with proliferation in endothelial cells more significant than smooth muscle cells. Apoptosis was not significant.Gene expression of TGF-beta1 and beta3 precedes arterial enlargement. Expression of apoptosis related factors is little regulated in the early stage of the flow-induced arterial remodeling.

Abstract

Duplex ultrasound scan (DUS) criteria for grading >50% carotid artery stenosis is typically divided into broad categories such as 50-79% stenosis, 80-99% stenosis, and occlusion. The purpose of this study is to validate DUS criteria for stratifying 50 to 100% carotid stenosis into 10% intervals using digital substraction cerebral angiography (DSCA) as the standard of comparison. Between 1996 and 2001, 163 patients were evaluated with duplex ultrasound and angiography. A total of 326 carotid arteries were studied using DUS in an accredited ICAVL vascular laboratory. Threshold velocity criteria for determining the degree of carotid stenosis was defined according to seven categories: <50%, 50-59%, 60-69%, 70-79%, 80-89%, 90-99%, and occlusion. Treatment decisions were based on the angiographic findings. In cases where the degree of stenosis as defined by duplex velocity criteria did not correlate with angiographically defined stenosis, each record was reviewed to determine whether the angiographic findings altered the surgeon's treatment decision. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for DUS-defined degree of stenosis as compared to angiographically defined stenosis were determined. There was a high correlation (R = 0.96) between duplex scan and angiography in 93% (302/326) of the cases. Clinical management was altered in only 3% (10/326) of the cases because of the results of angiography. The DUS velocity criteria to grade the severity of carotid disease in 10% intervals is reliable and accurate. Clinical management of patients with carotid stenosis can be based solely on carotid DUS in 97% of patients considered for treatment of carotid artery disease.

Abstract

To determine whether increasing experience with endovascular abdominal aortic aneurysm (AAA) repair in a single institution will result in improved outcome.A retrospective review was undertaken of 150 consecutive cases of endovascular AAA repairs performed using the AneuRx device between October 1996 and April 2000 in a university-based medical center. The population was divided into early and late groups of 75 patients each. Endpoints included technical success; complications; early (< or =30-day) morbidity, mortality and rupture; endoleak at discharge and at 1 month; early secondary intervention; proximal neck and iliac tortuosity; extender cuff placement; femoral reconstructions beyond primary repair; total fluoroscopy time; and contrast load.Baseline patient and aneurysm characteristics were similar between the 2 groups. Technical success was 98.7%; 2 cases were converted intraprocedurally owing to difficult iliac access (early group) and a severely angulated proximal neck (late group). There was a tendency toward more frequent use of intraoperative proximal extender cuffs in the early group (12% versus 4% in the late group, p=0.13). Femoral reconstructions were more frequent in the early group (36% versus 19%, p<0.025). While total contrast volume was similar (111 +/- 56 versus 105 +/- 45 mL, p=NS), total fluoroscopy time was significantly reduced (p<0.05) between the early and late groups.With attention to detail and careful patient selection, successful endovascular AAA repair can be achieved with very few conversions and low perioperative mortality even during the center's early experience. Evidence indicates, however, that a learning curve definitely exists, as shown by fewer access site problems, more accurate device deployments, and decreased fluoroscopy times as proficiency is attained.

Abstract

In planning operations for patients with cardiovascular disease, vascular surgeons rely on their training, past experiences with patients with similar conditions, and diagnostic imaging data. However, variability in patient anatomy and physiology makes it difficult to quantitatively predict the surgical outcome for a specific patient a priori. We have developed a simulation-based medical planning system that utilizes three-dimensional finite-element analysis methods and patient-specific anatomic and physiologic information to predict changes in blood flow resulting from surgical bypass procedures. In order to apply these computational methods, they must be validated against direct experimental measurements. In this study, we compared in vivo flow measurements obtained using magnetic resonance imaging techniques to calculated flow values predicted using our analysis methods in thoraco-thoraco aortic bypass procedures in eight pigs. Predicted average flow rates and flow rate waveforms were compared for two locations. The predicted and measured waveforms had similar shapes and amplitudes, while flow distribution predictions were within 10.6% of the experimental data. The average absolute difference in the bypass-to-inlet blood flow ratio was 5.4 +/- 2.8%. For the aorta-to-inlet blood flow ratio, the average absolute difference was 6.0 +/- 3.3%.

Abstract

To compare the outcomes of open versus endovascular repair of abdominal aortic aneurysm (AAA) in a cohort of patients who fulfill morphological criteria for endovascular repair.A retrospective review of 229 consecutive AAA patients treated over a 3-year period identified 149 patients who were candidates for endovascular repair based on preoperative computed tomography and angiography. Of the 149 patients, 79 (68 men; mean age 74 +/- 8 years) underwent endovascular repair with the AneuRx stent-graft; the remaining 70 (56 men; mean age 72 +/- 8 years) had open repair. Short-term outcome measures were 30-day mortality and procedure-related morbidity, length of stay in the intensive care unit and hospital, intraoperative blood loss, interval to oral diet, and time to ambulation. Long-term outcome measures included death and secondary procedures.There was no difference in the 30-day mortality between endovascular repair (2, 2.5%) and open repair (2, 2.9%), even though endovascular patients had more comorbidities (p<0.05). Overall length of stay was reduced for endovascular patients (3.9 +/- 2.4 days versus 7.7 +/- 3.1 days for surgical patients, p<0.0001). Fewer endograft patients had complications (24% versus 40% for open repair, p<0.05), and the severity of these complications was less, as evidenced by the shorter hospital stays for endovascular patients with complications compared to conventionally treated patients with complications (6.7 +/- 2.4 days versus 22.5 +/- 35.2 days, p<0.05). There were no aneurysm ruptures or late surgical conversions in either group.Patients with AAA who were endograft candidates but who were treated with open repair experienced more morbidity and had more complications than patients treated with stent-grafts. Despite increased comorbidities in the endograft patients, there was no increase in mortality compared to open repair. Both treatments required secondary procedures and appeared to be equally effective in preventing aneurysm rupture up to 3 years.

Abstract

Endoleaks and endotension are critically important complications of some endovascular aortic aneurysm repairs (EVARs). For the resolution of controversial issues and the determination of areas of uncertainty relating to these complications, a conference of 27 interested leaders was held on November 20, 2000.These 27 participants (21 vascular surgeons, five interventional radiologists, one cardiologist) had previously answered 40 key questions on endoleaks and endotension. At the conference, these 40 questions and participant answers were discussed and in some cases modified to determine points of agreement (consensus), near consensus (prevailing opinion), or disagreement.Conference discussion added two modified questions for a total of 42 key questions for the participants. Interestingly, consensus was reached on the answers to 24 of 42 or 57% of the questions, and near consensus was reached on 14 of 42 or 33% of the questions. Only with the answers to four of 42 or 10% of the questions was there persistent controversy or disagreement.The current endoleak classification system with some important modifications is adequate. Types I and II endoleak occur after 0 to 10% and 10% to 25% of EVARs, respectively. Many (30% to 100%) type II endoleaks will seal and have no detrimental effect, which never or rarely occurs with type I endoleaks. Not all endoleaks can be visualized with any technique, and increased pressure (endotension) can be transmitted through clot. Aneurysm pulsatility after EVAR correlates poorly with endoleaks and endotension. An enlarging aneurysm after EVAR mandates surgical or interventional treatment. These and other conclusions will help to resolve controversy and aid in the management of these vexing complications and should also point the way to future research in this field.

Abstract

The objective of this study was to evaluate gender differences in the selection, procedure, and outcome of endovascular abdominal aortic aneurysm repair (EVAR).Between October 1996 and January 2001, 378 patients were evaluated for EVAR and 189 patients underwent EVAR with the Medtronic AneuRx stent graft at a single center.Women constituted 17% of patients considered for EVAR. Their eligibility rate (49%) did not differ significantly from that of men (57%), and they constituted 14% of patients who underwent EVAR (26/189). Women who underwent EVAR were older (77.9 +/- 6.3 years versus 73.1 +/- 8.1 years; P

Abstract

To assess elastin biosynthesis in the aortic wall in response to acute elevation of blood pressure, we studied the aortic gene expression of tropoelastin in a rabbit midthoracic aortic coarctation model. The time points of the study were 1, 3, and 7 days and 2, 4, and 8 weeks after coarctation. Additional animals were subjected to hypercholesterolemia for analysis of tropoelastin expression in the intimal lesion. mRNA for tropoelastin was quantitated by Northern blot analysis and its distribution was revealed by in situ hybridization. The 65-kDa tropoelastin was analyzed by Western blotting and immunohistochemistry. Tropoelastin mRNA proximal to the coarctation was increased at 2 weeks and returned to baseline by 8 weeks (P < 0.05 versus control). Changes in 65-kDa tropoelastin corresponded to those of mRNA. Tropoelastin gene was expressed mainly in the intima and in the outer media at the proximal region to the stenoses, which was particularly remarkable in the intimal lesion. The results indicate that tropoelastin gene expression was enhanced in the early remodeling response to elevated blood pressure. The distribution of newly synthesized tropoelastin in the outer media suggests a reenforcement role of tropoelastin, which preserves mechanical resiliency in response to changes in tensile stress.

Abstract

Arterial intimal thickening is consisted of predominately smooth muscle cells (SMC). The source of these SMCs and mechanisms response for their changes have not been well cleared. Using a model of rabbit common carotid artery (CCA) shear induced intimal thickening, we sought to identify and describe the source of SMCs in intima. The enlarged CCA 28 days after arteriovenous fistula (AVF) creation was subjected to subnormal wall shear stress (WSS) for 1, 3, and 7 days by closure of the AVF. To determine SMC proliferation, BrdU pulse labeling of SMCs was performed. BrdU-labeled SMCs were tracked over time to further confirm SMC migration. In response to subnormal WSS intimal thickening developed progressively. BrdU-labeled SMCs localized in the subendothelial area. When the BrdU-labeled medial SMCs were tracked 1 day after AVF closure, progenies of these BrdU-incorporated SMCs increased by 4.8-fold with 75% of them in the intima. They were 12-fold increased with 83% in the intima 7 days after. En face examination showed an accumulation of SMCs in internal elastic lamina gap after AVF closure, which later migrated into subendothelial area. In situ hybridization revealed increased TGF-beta1 mRNA expression in intimal SMCs. This study demonstrates that the medial SMCs are the predominant cells in subnormal WSS-induced intimal thickening. Early expression of TGF-beta1 may play an important role in the process of intimal thickening.

Abstract

To determine the feasibility of using magnetic resonance imaging (MRI) to non-invasively measure strain in the aortic wall.Cine phase contrast MRI was used to measure the velocity of the aortic wall and calculate changes in circumferential strain over the cardiac cycle. A deformable vessel phantom was used for initial testing and in vitro validation. Ultrasonic sonomicrometer crystals were attached to the vessel wall and used as a gold standard.In the in vitro validation, MRI-calculated wall displacements were within 0.02 mm of the sonomicrometer measurements when maximal displacement was 0.28 mm. The measured maximum strain in vitro was 0.02. The in vivo results were on the same order as prior results using ultrasound echo-tracking.Results of in vivo studies and measurement of cyclic strain in human thoracic and abdominal aortas demonstrate the feasibility of the technique.

Abstract

Late onset graft or attachment site-related endoleaks may be hazardous, and early identification of patients at risk is important. We describe a patient who underwent implantation of a bifurcated stent graft 5.5 cm below the renal arteries because of a technical error with three extender cuffs implanted proximally to bridge the gap. During the 1st year, aneurysm diameter decreased from 68 to 52 mm. After 1 year, the patient had an acute endoleak develop, which originated between two of the extender cuffs and which was accompanied by severe abdominal pain and reexpansion of the aneurysm. This endoleak was treated with insertion of an additional bifurcated stent graft within the extender cuff segment. The patient has been subsequently followed for 6 months and has had no endoleak or symptoms, and aortic diameter has decreased once again to 55 mm.

Abstract

To present a unique demonstration of postoperative perigraft contrast masquerading as an endoleak following endovascular abdominal aortic aneurysm (AAA) repair.A 66-year-old man underwent endovascular stent-graft repair of a 4.6-cm infrarenal AAA. The procedure was uncomplicated, and intraoperative completion angiography demonstrated good proximal and distal fixation of the stent-graft without an endoleak. A spiral computed tomographic (CT) angiogram obtained on postoperative day 2 revealed a large amount of extrastent contrast along the posterior aspect of the aneurysm sac. This defect had the appearance of an endoleak, but it was also present on the non-contrast images. A color-flow duplex examination performed on the same day showed a widely patent stent-graft with no evidence of extrastent flow.Contrast trapped in the aneurysm sac during endovascular aneurysm repair may be misinterpreted as an endoleak on postprocedural CT scans. "Pseudoendoleaks" can be distinguished from true endoleaks by examination of prebolus, noncontrast CT images, as well as by duplex ultrasound scanning.

Abstract

Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses.The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft.The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.

Abstract

To evaluate the impact of a change in the manufacturing of the AneuRx stent-graft on the long-term results of endovascular abdominal aortic aneurysm (AAA) repair.The first 70 AAA patients treated with the AneuRx stent-graft between October 1996 and December 1998 were reviewed. The early stiff bifurcated design (STIFF) was used in 23 patients (mean age 71.7 +/- 9.3 years, range 45-87) and the current flexible bifurcated design (FLEX) in 47 mean age 75.0 +/- 7.3 years, range 61-96). Data on patient demographics, aneurysm morphology, technical success, complications, secondary procedures, and outcomes were compared using Kaplan-Meier estimates to evaluate patient survival and freedom from surgical conversion, rupture, and secondary interventions at 6, 12, and 24 months.The 2 groups were equally matched with regard to age, preoperative comorbidities, proximal neck dimensions, and aneurysm diameter. Mean follow-up times were 22.42 +/- 11.72 months (range 1-46) for the STIFF cohort and 18.08 +/- 6.14 months (range 1-30) for the FLEX (p = 0.057). Eleven (48%) of 23 STIFF patients required secondary interventions versus 6 (13%) of 47 FLEX patients (p < 0.05). There were no ruptures. At the 24-month interval, survival estimates were 86% for STIFF and 76% for FLEX (p = NS); freedom from surgical conversion was 100% for STIFF and 97% for FLEX (p = NS) and freedom from secondary interventions was 18% for STIFF and 90% for FLEX (p < 0.05) at 24 months.The AneuRx stent-graft was effective in achieving the primary objective of preventing aneurysm rupture in all patients. However, increasing the flexibility of the bifurcated module significantly improved the primary success rate by reducing the need for subsequent secondary interventions.

Abstract

The purpose of this study was to determine the impact of an endovascular stent-graft program on vascular training in open aortic aneurysm surgery.The institutional and vascular surgery fellow experience in aortic aneurysm repair during a 6-year period was reviewed. The 3-year period before introduction of endovascular repair was compared with the 3-year period after introduction of endovascular repair. All patients undergoing abdominal aortic aneurysm (AAA) or thoracoabdominal aortic aneurysm repairs were entered prospectively into a vascular registry and retrospectively analyzed to evaluate the changing patterns in aortic aneurysm treatment and surgical training.Between July 1994 and June 2000, a total of 588 patients with AAA or thoracoabdominal aneurysms were treated at Stanford University Medical Center. There were 296 (50%) open infrarenal AAA repairs, 87 (15%) suprarenal AAA repairs, 47 (8%) thoracoabdominal aneurysm repairs, and 153 (26%) endovascular stent-grafts. The total number of aneurysms repaired per year by vascular fellows before the endovascular program was 71.3 +/- 4.9 (range, 68-77) and increased to 124.7 +/- 35.6 (range, 91-162) after introduction of endovascular repair (P

Abstract

The purpose of this study was to examine the effect of aortoiliac tortuosity, as assessed by observers and 3-dimensional (3D) computer-based methods, on the conduct and outcome of endovascular repair of abdominal aortic aneurysms.Infrarenal aortoiliac tortuosity was measured in 75 patients (mean follow-up, 14.8 +/- 10.4 months) who underwent endovascular repair of abdominal aortic aneurysms by using the following four methods: (1) grading by 2 experienced observers; (2) tortuosity index measured as the inverse radius of curvature (cm(-1)) at 1-mm intervals along the median luminal centerline (MLC) on 3D reconstructions of computed tomography (CT) angiograms and was calculated as the sum of values greater than 0.3 cm(-1); (3) MLC-straight line length ratio from renal to hypogastric arteries; (4) manual measurement of angles at points of angulation on anteroposterior and lateral projections of 3D CT reconstructions. In evaluating association between these measures, correlation between human observers was accepted as the gold standard.For rating of overall aortoiliac tortuosity, interobserver correlation (r = 0.67) was comparable with correlation of observers with tortuosity index (r = 0.67 and 0.56), whereas correlations of each observer with MLC-straight line ratio (r = 0.50 and 0.56) and cumulative angulation (r = 0.44 and 0.44) were significant but weaker. For determining the relative tortuosity of right and left aortoiliac access, agreement between observers and tortuosity index (54% and 58%; P < .05; kappa, 0.33 and 0.38) was not as good as between observers (68%; P < .001; kappa, 0.53). This difference was primarily related to evaluation of the aorta, where interobserver correlation (r = 0.71) was better than that between each observer and tortuosity index (r = 0.47 and 0.55), whereas correlations in the iliac arteries were comparable (r = 0.64 and 0.67) (all coefficients P < .01). Increased tortuosity was associated with a more complex endovascular repair, as reflected by longer fluoroscopy time (P = .05), use of more contrast material (P = .03), use of extender modules (P = .04), and more frequent use of arterial reconstruction (P = .01), but was not associated with a higher overall complication rate. Increased tortuosity, when it occurred in the aortic neck, was associated with predischarge endoleak (P = .03) but not with late endoleak, intervention, or aneurysm-related adverse events.Aortoiliac tortuosity is associated with increased complexity of endovascular aneurysm repair and with predischarge endoleak but does not appear to affect intermediate-term results. Computer-based 3D measurement of aortoiliac tortuosity is feasible and clinically meaningful. Its ultimate role in relation to human assessment must be further defined in future studies.

Abstract

To determine the significance of persistent type-II endoleaks and whether they can be predicted preoperatively in patients with abdominal aortic aneurysms (AAA).The charts of all AAA patients treated with the AneuRx stent-graft at a single center from 1996 to 1998 were reviewed. Patients with <12-month follow-up or type-I endoleaks were excluded. The presence or absence of type-II endoleaks was determined from duplex imaging and computed tomographic angiography. Three groups were identified and compared: 16 patients with persistent type-II endoleaks (PE), 14 patients with transient type-II endoleaks (TE), and 16 patients with no endoleak (NE).The groups did not differ with regard to age, preoperative comorbidities, follow-up time, and AAA neck diameter and length. AAA diameters were 57.1 +/- 9.0 mm for NE, 63.4 +/- 11.4 mm for TE, and 55.6 +/- 4.2 mm for PE. The inferior mesenteric artery (IMA) was patent in 5 (31%) NE patients, 6 (43%) TE patients, and 13 (81%) PE patients (p < 0.01). The number of patent lumbar arteries visualized preoperatively was 0.5 +/- 1.0 in NE, 1.3 +/- 0.8 in TE, and 2.4 +/- 0.6 in PE (p < 0.0001). Patent IMAs (RR 0.82, p < 0.01) and >2 lumbar arteries (RR 0.40, p < 0.0001) were identified as independent preoperative risk factors for persistent endoleaks. There were no changes in mean diameter or volume in aneurysms with persistent endoleaks.No adverse clinical events were related to the presence of type-II endoleaks, but there was no decrease in aneurysm size in patients with persistent type-II leaks. Patients with a large, patent IMA, or >2 lumbar arteries on preoperative CT angiography are at higher risk for persistent type-II endoleaks.

Abstract

We investigated apoptosis of endothelial cells during the arterial narrowing process in response to reduction in flow. The decrease in flow was created in the carotid artery by closure of an arteriovenous fistula (AVF), which had been established for 28 days in rabbits. The endothelial cell apoptosis in the carotid artery was studied at 1, 3, 7, and 21 days of flow reduction after closure of the AVF by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with laser scanning confocal microscopy and transmission and scanning electron microscopy. After AVF closure, arterial lumen diameter was reduced by 36%, and compared with endothelial cells before the closure, the number of endothelial cells was decreased by 45% at 21 days. Endothelial cell apoptosis was observed at 1 day, peaked at 3 days (381.3+/-87.1 cells per square millimeter), and decreased at 7 days. These cells had irregular protrusions under scanning electron microscopy and were characterized by fragmented nuclei under transmission electron microscopy. Apoptotic cells were mainly beneath the endothelium and were occasionally within smooth muscle cells and endothelial cells. The results suggest that apoptosis of endothelial cells may play a role in the arterial remodeling in response to a reduction in flow.

Abstract

The purpose of this study was to determine the long-term functional outcome after unilateral hypogastric artery occlusion during endovascular stent graft repair of aortoiliac aneurysms.During a 41-month period, 157 consecutive patients underwent elective endovascular stent graft repair of aortoiliac aneurysms with the Medtronic AneuRx device. Postoperative computed tomography scans were compared with preoperative scans to identify new hypogastric artery occlusions. Twenty-three (15%) patients had unilateral hypogastric occlusion, and there were no cases of bilateral occlusions. Telephone interviews about past and current levels of activity and symptoms were conducted, and pertinent medical records were reviewed. All 23 (100%) patients were available for the telephone interview. A disability score (DS) was quantitatively graded on a discrete scale ranging from 0 to 10 corresponding to "virtually bed-bound" to "greater-than-a-mile" exercise tolerance. Worsening or improvement of symptoms was expressed as a difference in DS between two time points (-, worsening/+, improving).Among the 23 patients, two groups were identified: 10 patients (43%) had planned and 13 patients (57%) had unplanned or inadvertent occlusions. The patients in the two groups did not differ significantly in the mean age (73.4 vs 73.7 years), sex (male:female, 9:1 vs 10:3), and duration of follow-up (15.6 vs 14.4 months). Nine (39%) of the 23 patients, five patients in the planned and four patients in the unplanned group, reported significant symptoms of hip and buttock claudication ipsilateral to their occluded hypogastric arteries. The mean decrement from baseline of these nine patients in their DS postoperatively was -3.3. The symptoms were universally noted on postoperative day 1. Although most patients improved (89%), one (11%) never got better. Among those whose symptoms improved, the mean time to improvement was 15 weeks, but with a plateau thereafter resulting in a net decrement of DS of -2.3 from baseline. Finally, when questioned whether they would undergo the procedure again, all 23 patients unanimously answered, "Yes."A significant number (39%) of patients who sustain hypogastric artery occlusion after endovascular aneurysm repair have symptoms. Although most patients with symptoms have some improvement, none return to their baseline level of activity. Despite this, all patients in retrospect would again choose endovascular repair over conventional open repair.

Abstract

The purpose of this study was to evaluate our experience with the diagnosis and management of vascular injuries in a group of high-performance athletes.Between June 1994 and June 2000, we treated 26 patients who sustained vascular complications as a result of athletic competition. Clinical presentation, type of athletic competition, location of injury, type of therapy, and degree of rehabilitation were analyzed retrospectively.The mean age of the patients was 23.8 years (range, 17-40). Twenty-one (81%) patients were men, and five (19%) were women. Athletes included 8 major-league baseball players, 7 football players, 2 world-class cyclists, 2 rock climbers, 2 wind surfers, 1 swimmer, 1 kayaker, 1 weight lifter, 1 marksman, and 1 volleyball player. There were 14 (54%) arterial and 12 (46%) venous complications. Arterial injuries included 7 (50%) axillary/subclavian artery or branch artery aneurysms with secondary embolization, 6 (43%) popliteal artery injuries, and 1 (7%) case of intimal hyperplasia and stenosis involving the external iliac artery. Subclavian vein thrombosis (SVT) accounted for all venous complications. Five of the seven patients with axillary/subclavian branch artery aneurysms required lytic therapy for distal emboli, and six required operative intervention. All popliteal artery injuries were treated by femoropopliteal bypass graft with autogenous saphenous vein. The external iliac artery lesion, which occurred in a cyclist, was repaired with limited resection and vein patch angioplasty. All 12 patients with SVT were treated initially with lytic therapy and anticoagulation. Eight patients required thoracic outlet decompression and venolysis of the subclavian vein. Thirteen arterial reconstructions have remained patent at an average follow-up of 31.9 months (range, 2-74). One patient with a popliteal artery injury required reoperation at 2 months for occlusion of his bypass graft. Eleven of the patients with an arterial injury were able to return to their prior level of competition. All of the patients with SVT have remained stable without further venous thrombosis and have returned to their usual level of activity.Athletes are susceptible to a variety of vascular injuries that may not be easily recognized. A high level of suspicion, a thorough workup including noninvasive studies and arteriography/venography, and prompt treatment are important for a successful outcome.

Abstract

Aortic aneurysms usually develop in the atherosclerosis prone infrarenal abdominal aorta. To assess the role of atherosclerosis in aortic enlargement, we studied the relation between plaque formation and aortic size in 30 pressure-fixed male cadaver aortas (age 40-95 years, mean age 67 years). Morphometric analysis of transverse sections of the mid-thoracic and the mid-abdominal aortas included measurement of intimal plaque area, lumen area, plaque and media thicknesses. The area encompassed by the internal elastic lamina area (IEL area) was taken to be an index of aortic size. IEL area increased with age at both the thoracic (r=0.77, P<0.01) and abdominal (r=0.54, P<0.01) aortic levels. The aorta also enlarged with increasing plaque area at the thoracic (r=0.73, P<0.01) and abdominal (r=0.79, P<0.01) levels. Regression analysis of IEL area on age, body weight, height and plaque area revealed that the primary predictor of thoracic aortic size was age, whereas the primary predictor of abdominal aortic size was plaque area. Plaque thickness in the abdominal aorta was greater than in the thoracic aorta (P<0.01). Increased plaque area was associated with a significant decrease in media thickness in the abdominal aorta (r=-0.75, P<0.01) but not in the thoracic aorta. Aortas with relatively enlarged abdominal segments, i.e. those with a thoracic to abdominal ratio of <1.2 (n=13), were compared to those with a normal ratio (> or =1.2, n=17). Relatively large abdominal aortas had twofold greater plaque area (P<0.001), reduced medial thickness (P<0.05), fewer medial elastic lamellae (P<0.01) and greater mural tensile stress (P<0.05) than relatively normal abdominal aortas. We conclude that plaque formation in the infrarenal abdominal aorta in humans is associated with aortic enlargement and decreased media thickness. These changes may be predisposing factors for the preferential development of subsequent aneurysmal dilation in the abdominal aorta.

Abstract

Despite successful surgical revascularization of ischemic limbs, a local and systemic reperfusion injury may occur after normal blood reperfusion. Recent experimental and clinical application of controlled limb reperfusion in Europe has demonstrated superior results, with lower morbidity and mortality. This new surgical technique includes modification of the reperfusate (calcium, pH, substrates, osmolarity, free radical scavenger) and the circumstances of initial reperfusion (time, temperature, pressure). This report describes the first application of controlled limb reperfusion after reperfusion injury. A 16-year-old boy underwent femoral access cardiopulmonary bypass for repeat cardiac repair with an ischemic time of 245 minutes. Postoperatively, severe ischemia/reperfusion syndrome developed with muscle contracture, immobility, and anesthesia of the right leg with a second ischemic time of about 6 hours. The systemic creatine phosphokinase level was 88,000 U/L; myoglobin was 27,000 ng/mL. He underwent controlled limb reperfusion by withdrawing blood from the aorta and mixing it with a crystalloid solution (calcium-reduced, hyperosmolar, hyperglycemic, alkalotic, glutamate- and aspartate-enriched, and containing a free radical scavenger) under controlled conditions (blood:crystalloid solution 6:1, for 30 minutes, reperfusion pressure < 50 mm Hg, and normothermia) before establishing normal blood reperfusion. Metabolic data from the central and femoral vein demonstrated a significant reduction of all previous elevated enzyme levels, avoidance of hyperkalemia, normalization of acidosis, and avoidance of systemic reperfusion injury with no multiorgan failure. Limb salvage was accomplished and functional recovery almost complete. To the authors' knowledge, this is the first application of controlled limb reperfusion reported in North America. With this surgical technique we were able to prevent metabolic local and systemic reperfusion changes after prolonged ischemia and also reduced previous reperfusion changes. This report confirms former experimental data, and further clinical studies are warranted.

Abstract

The molecular basis of vascular response to hypertension is largely unknown. Both cellular and extracellular components are critical. In the current study we tested the hypothesis that there is a balance between vascular cell proliferation and cell death during vessel remodeling in response to hypertension.A midthoracic aortic coarctation was created in rats to induce an elevation of blood pressure proximal to the coarctation. The time course was 1 and 3 days and 1, 2, and 4 weeks for the study of the proximal aorta. Ribonuclease protection assay and Western blot analysis were used to evaluate gene expression of growth and apoptosis-related cytokines with two sets of multiple probes, rCK-3 and rAPO-1. Cell proliferation was determined with BrdU (5-bromo-2'-deoxyuridine) incorporation. Apoptosis was examined with TUNEL (transferase-mediated dUTP nick end-labeling). Morphometry was performed on histologic sections.Coarctation produced hypertension in the proximal aorta, 118 +/- 9 mm Hg versus 94 +/- 6 mm Hg in controls (P

Abstract

The purpose of this study was to determine whether radiographically demonstrated proximal stent graft contour can be used as a marker for security of proximal neck fixation after endovascular aneurysm repair.Stent graft structure was examined in 100 consecutive patients with abdominal aortic aneurysms who were treated with the stent graft. Stent graft integrity, stent contour, angulation, compression, and position were assessed by use of plain abdominal radiography, and the results were correlated with contrast computed tomography (CT) scanning, clinical findings, and outcomes. Repeated imaging was carried out during follow-up of 3 to 38 (mean, 12) months.Stent graft repair was successful in all 100 patients. No stent fractures were identified. Concentric compression of the proximal portion of the stent graft was visible in 69% of patients and reflected deliberate oversizing of the stent graft at the time of implantation. In 5% of patients, a short eccentric compression deformity of the proximal stent was observed. This finding was associated with an increased risk of stent graft migration (P

Abstract

The objective was to review the current results of endovascular abdominal aortic aneurysm repair with the AneuRx stent graft and to determine the effectiveness of the device in achieving the primary objective of preventing aneurysm rupture.The outcome of all patients treated during the past 4 years in the U.S. AneuRx clinical trial was determined, and the worldwide clinical experience was reviewed.A total of 1192 patients were treated with the AneuRx stent graft during all phases of the U.S. Clinical Trial from June 1996 to November 1999, with follow-up extending to June 2000. Ten (0.8%) patients have had aneurysm rupture, with most ruptures (n = 6) occurring in 174 (3.4%) patients treated with an early stiff bifurcation stent graft design used in phase I and in the initial stages of phase II. Since the current, flexible, segmented bifurcation stent graft design was introduced, four (0.4%) ruptures have occurred among 1018 patients treated. Of these, one was during implantation, two were placed too far below the renal arteries, and one patient refused treatment of a type I endoleak. Kaplan-Meier analysis of all 1192 patients treated with the AneuRx stent graft including both stent graft designs revealed the patient survival rate to be 93% at 1 year, 88% at 2 years, and 86% at 3 years, freedom from conversion to open repair to be 98% at 1 year, 97% at 2 years, and 93% at 3 years, and freedom from secondary procedure to be 94% at 1 year, 92% at 2 years, and 88% at 3 years. Freedom from aneurysm rupture with the commercially available segmented bifurcation stent graft was 99.7% at 1 year, 99.5% at 2 years, and 99.5% at 3 years. The presence or absence of endoleak on contrast computed tomography scanning after stent graft placement was not found to be a significant predictor of long-term outcome measures. Worldwide experience with the AneuRx device now approaches 10,000 patients.Endovascular management of abdominal aortic aneurysms with the AneuRx stent graft has markedly reduced the risk of aneurysm rupture while eliminating the need for open aneurysm surgery in 98% of patients at 1 year and 93% of patients at 3 years. The device was effective in preventing aneurysm rupture in 99.5% of patients over a 3-year period. The overall patient survival rate was 93% at 1 year and 86% at 3 years.

Abstract

The purpose of this study was to assess atherosclerotic plaque deposition and aortic wall responses in the abdominal aorta in relation to the development of aneurysmal and occlusive disease in the infrarenal aorta.Morphologic differences at five standardized locations in the infrarenal aorta in 67 pressure perfusion-fixed male cadaver aortas (aged, 41-98 years; mean, 66 years) were studied and compared with the supraceliac segment. Quantitative computer-assisted morphometry of histologic sections included measurement of plaque area, lumen area, lumen diameter, media thickness, number of medial elastic lamellae, and the area encompassed by the internal elastic lamina that best represents the artery size of each segment. The ratio of the supraceliac segment to the midabdominal segment (normally greater than 1.3) was used to define three groups: Group I (normal): ratio greater than or equal to 1.30 (n = 31); Group II (intermediate): ratio greater than or equal to 1.20 but less than 1.30 (n = 20); and Group III: ratio less than 1.20 (n = 16), which represented dilated midabdominal aortas. There was no significant difference in age among the groups.Group I had minimal intimal plaque and little gross evidence of atherosclerosis. Group II had increased intimal plaque compared with Group I (P

Abstract

We conducted a novel quantitative three-dimensional analysis of computed tomography (CT) angiograms to establish the relationship between aortic geometry and age, sex, and body surface area in healthy subjects.Abdominal helical CT angiograms from 77 healthy potential renal donors (33 men/44 women; mean age, 44 years; age range, 19-67 years) were selected. In each dataset, orthonormal cross-sectional area and diameter measurements were obtained at 1-mm intervals along the automatically calculated central axis of the abdominal aorta. The aorta was subdivided into six consecutive anatomic segments (supraceliac, supramesenteric, suprarenal, inter-renal, proximal infrarenal, and distal infrarenal). The interrelated effects of anatomic segment, age, sex, and body surface area on cross-sectional dimensions were analyzed with linear mixed-effects and varying-coefficient statistical models.We found that significant effects of sex and of body surface area on aortic diameters were similar at all anatomic levels. The effect of age, however, was interrelated with anatomic position, and gradually decreasing slopes of significant diameter-versus-age relationships along the aorta, which ranged from 0.14 mm/y (P

Abstract

To examine whether complete aneurysm exclusion is a reliable marker for successful long-term endovascular abdominal aortic aneurysm (AAA) repair.The medical records, computed tomographic (CT) scans, and duplex examinations of all the patients who underwent endovascular AAA repair at a single institution and had at least 12 months of follow-up were reviewed. Sixty-seven patients (58 men; mean age 74 years, range 57-87) were identified. Complete aneurysm exclusion was defined by the absence of an endoleak at any time before an adverse event. The primary endpoint included all major adverse events that occurred during the postoperative period, including aneurysm expansion, acute symptoms referable to the AAA, late secondary procedures, ruptures, and deaths from ruptures and all other causes.There were 44 adverse events (8 expanding aneurysms, 4 acute symptoms, 17 secondary procedures, and 15 deaths from other causes) in 28 (42%) patients. Among 36 (54%) patients who had initial complete aneurysm exclusion (no endoleak), 12 (33%) experienced adverse events, compared with 16 (52%) events in 31 patients who had endoleak (chi2 = 1.59, p = 0.21).There was no statistically significant difference in adverse events based on the presence or absence of endoleak. Complete aneurysm exclusion as defined by absence of an endoleak does not indicate an event-free postoperative course. A better marker of clinical success of endovascular AAA repair is needed.

Abstract

The purpose of this study was to compare duplex ultrasound scanning and computed tomographic (CT) angiography for postoperative imaging and surveillance after endovascular repair of abdominal aortic aneurysm (AAA).One hundred consecutive patients with AAA underwent endovascular (Medtronic AneuRx, stent graft) aneurysm repair and were imaged with both CT angiography and duplex ultrasound scanning at regular intervals after the procedure. Each imaging modality was evaluated for technical adequacy and for documentation of aneurysm size, endoleak, and graft patency. In concurrent scan pairs, accuracy of duplex scanning was compared with CT.A total of 268 CT scans and 214 duplex scans were obtained at intervals of 1 to 30 months after endovascular aneurysm repair (mean follow-up interval, 9+/-7 months). All CT scans were technically adequate, and 198 (93%) of 214 duplex scans were technically adequate for the determination of aneurysm size, presence of endoleak, and graft patency. Concurrent (within 7 days of each other) scan pairs were obtained in 166 instances in 76 patients (1-6 per patient). The maximal transverse aneurysm sac diameter measured with both methods correlated closely (r = 0.93; P

Abstract

We studied the mural distribution of collagen types I and III and tropoelastin in enhanced experimental atherogenesis induced in rabbits by hyperlipidemia superimposed by hypertension. Animals were fed a high-cholesterol diet for 5 weeks and also subjected to midthoracic aortic coarctation for 4 weeks. Serum cholesterol levels were increased and blood pressure was elevated proximal to the coarctation. Foam cell lesions developed in the aorta proximal to the coarctation. In situ hybridization and immunohistochemistry showed that gene expression of collagen types I and III and tropoelastin was upregulated, with a differential distribution across the arterial wall. New collagen type I was mainly distributed in the intima, the outer media, and the adventitia. New collagen type III was spread more uniformly across the wall, including the adventitia, whereas tropoelastin was mainly localized in intimal foam cell lesions. Morphometric data showed an increase in wall thickness. These results suggest that collagen types I and III play a role in remodeling of the aortic wall in response to hypertension. The remarkable involvement of the adventitia in this response indicates that the adventitia is an important component of the arterial wall. Tropoelastin is closely associated with foam cell lesion formation, suggesting a role for this component in atherogenesis as well.

Abstract

To evaluate of the impact of endovascular aneurysm repair on the rate of open surgical repair and on the overall treatment of abdominal aortic aneurysms (AAAs).All patients with AAA who were treated during two consecutive 40-month periods were reviewed. During the first period, only open surgical repair was performed; during the subsequent 40 months, endovascular repair and open surgical repair were treatment options.A total of 727 patients with AAA were treated during the entire period. During the initial 40 months, 268 patients were treated with open surgical repair, including 216 infrarenal (81%), 43 complex (16%), and 9 ruptured (3%) aortic aneurysms. During the subsequent 40 months, 459 patients with AAA were treated (71% increase). There was no significant change in the number of patients undergoing open surgical repair and no significant difference in the rate of infrarenal (238 [77%]) and complex (51 [16%]) repairs. A total of 353 patients were referred for endovascular repair. Of these, 190 (54%) were considered candidates for endovascular repair based on computed tomography or arteriographic morphologic criteria. Analyzing a subgroup of 123 patients, the most common primary reasons for ineligibility for endovascular repair were related to morphology of the neck in 80 patients (65%) and of the iliac arteries in 35 patients (28%). A total of 149 patients underwent endovascular repair. Of these, the procedure was successful in 147 (99%), and 2 (1%) patients underwent surgical conversion. The hospital death rate was 0%, and the 30-day death rate was 1%. During a follow-up period of 1 to 39 months (mean 12 +/- 9), 21 secondary procedures to treat endoleak (20) or to maintain graft limb patency (1) were performed in 17 patients (11%). There were no aneurysm ruptures or aneurysm-related deaths.Endovascular repair appears to have augmented treatment options rather than replaced open surgical repair for patients with AAA. Patients who previously were not candidates for repair because of medical comorbidity may now be safely treated with endovascular repair.

Abstract

Hypertension is a well-known risk factor for coronary artery disease and carotid and lower extremity occlusive disease. Surgically induced hypertension in hypercholesterolemic animals results in increased aortic wall motion and increased plaque formation. We tested the hypothesis that reduction in aortic wall motion, despite continued hypertension, could reduce plaque formation. New Zealand White rabbits (n=26) underwent thoracic aortic banding to induce hypertension and were fed an atherogenic diet for 3 weeks. In 13 rabbits, a segment of aorta proximal to an aortic band was externally wrapped to reduce wall motion. All animals were fed an atherogenic diet for 3 weeks. Four groups were studied: 1, coarctation control (no wrap, n=7); 2, coarctation with loose wrap (n=6); 3, coarctation with firm wrap (n=7); and 4, control (noncoarcted, n=6). Wall motion, blood pressure, and pulse pressure were measured at standard reference sites proximal and distal to the coarctation by use of intravascular ultrasound. Quantitative morphometry was used to measure intimal plaque. Mean arterial pressure and cyclic aortic wall motion were equally increased proximal to the aortic coarctation in all 3 coarcted rabbit groups compared with the control group (P:<0.001). Wall motion in the segment of aorta under the loose and firm wraps was no different from the control value. The external wrap significantly reduced intimal thickening in the 4 groups by the following amounts: group 1, 0.30+/-0.03 mm(2); group 2, 0.06+/-0.02 mm(2); group 3, 0. 04+/-0.02 mm(2); and group 4, 0.01+/-0.01 mm(2) (P:<0.001). Localized inhibition of aortic wall motion in the lesion-prone hypertensive aorta resulted in significant reduction in intimal plaque formation. These data suggest that arterial wall cyclic motion may stimulate cellular proliferation and lipid uptake in experimental atherosclerosis.

Abstract

The purpose of this study was to determine the rate of eligibility among patients with abdominal aortic aneurysms (AAAs) considered for endovascular repair and to examine the effect of an endovascular program on the institutional pattern of AAA repair.All patients evaluated for endovascular AAA repair since the inception of an endovascular program were reviewed for determination of eligibility rates and eventual treatment. Open AAA repairs were categorized as simple (uncomplicated infrarenal), complex (juxtarenal, suprarenal, thoracoabdominal, infected), or ruptured, and their rates before and after initiation of an endovascular program were compared.Over 3 years, 324 patients were considered for endovascular AAA repair; 176 (54%) were candidates, 138 (43%) were not candidates, and 10 (3%) did not complete the evaluation. The rate of eligibility increased significantly from 45% (66/148 patients) during the first half of this period to 63% (110/176 patients) during the second half (P

Abstract

Surgeon-directed institutional peer review, associated with positive physician feedback, can decrease the morbidity and mortality rates associated with carotid endarterectomy.Case series.Tertiary care university teaching hospital.All patients undergoing carotid endarterectomy at our institution during a 5-year period ending August 1998.Stroke rate decreased from 3.8% (1993-1994) to 0% (1997-1998). The mortality rate decreased from 2.8% (1993-1994) to 0% (1997-1998). Length of stay decreased from 4.7 days (1993-1994) to 2.6 days (1997-1998). The total cost decreased from $13,344 (1993-1994) to $9548 (1997-1998).An objective, confidential peer review process that provides ongoing feedback of performance to surgeons and documents that performance in relationship with that of peers seems to be effective in reducing the morbidity and mortality rate associated with carotid endarterectomy. In addition, the review process lowered the hospital cost of performing carotid endarterectomy.

Abstract

The purpose of this study was to determine whether evidence of blood flow in the aneurysm sac (endoleak) is a meaningful predictor of clinical outcome after successful endovascular aneurysm repair.We reviewed all patients in Phase II of the AneuRx Multicenter Clinical Trial with successful stent graft implantation and predischarge contrast computed tomographic (CT) imaging. The clinical outcome of patients with evidence of endoleak was compared with the outcome of patients without evidence of endoleak. The CT endoleak status before hospital discharge at 6, 12, and 24 months was determined by each clinical center as well as by an independent core laboratory. Endoleak status at 1 month was assessed with duplex scanning examination or CT at each center without confirmation by the core laboratory.Centers reported endoleaks in 152 (38%) of 398 patients on predischarge CT, whereas the core laboratory reported endoleaks in 50% of these patients (P

Abstract

The purpose of this study was to determine the cause and frequency of aneurysm rupture after endovascular aneurysm repair.We reviewed each patient who sustained aneurysm rupture among all patients enrolled for endovascular aortic aneurysm repair in phases I, II, and III of the US AneuRx Multicenter Clinical Trial from June 1996 through October 1999.A total of 1067 patients were enrolled for endovascular aneurysm repair. The AneuRx stent graft was successfully implanted in 1046 patients (98%). Endovascular repair was unsuccessful in 21 patients (2%); 13 patients (1%) were converted to open aneurysm repair. Among these, two patients (0.2%) sustained aneurysm rupture due to procedure-related instrumentation and underwent open surgical conversion. Aneurysm rupture has occurred in seven patients (0.7%) 3 weeks to 24 months (mean, 16 months) after successful endovascular repair. Four patients survived open surgical repair, and three patients died within 30 days. Overall rupture-related mortality was 0.5% and included late deaths after rupture. Before rupture, two patients had endoleak and aneurysm enlargement, and five patients had no endoleak and no aneurysm enlargement. After aneurysm rupture all seven patients had evidence suggesting that there was poor fixation of the stent graft at the proximal distal, or iliac junction fixation sites. The two patients with endoleak declined recommended open surgical or endovascular repair, which could have prevented aneurysm rupture. In retrospect, the five patients without endoleak could potentially have avoided rupture with better patient selection, better stent graft positioning, or reinforcement of fixation points with stent graft extenders. The probability of no aneurysm rupture for all patients undergoing endovascular repair is 0.996 +/- 0.002 at 1 year and 0.974 +/- 0.011 at 2 years by life table analysis with the longest follow-up of 41 months.The early risk of aneurysm rupture after endovascular aneurysm repair is low. However, the possibility of rupture persists even in patients with no endoleak after the procedure. Therefore, all patients treated with endovascular aneurysm repair should continue to be monitored after the procedure. Patients with evidence suggesting insecure stent graft fixation should undergo further endovascular treatment or open surgical repair.

Abstract

To assess the effects on the biosynthesis of collagen types I and III associated with an acute increase in blood pressure, we established a mid-thoracic aortic coarctation in the rabbit and studied gene expression and protein accumulation of these collagen types proximal to the stenosis 1, 3 and 7 days and 2, 4 and 8 weeks after coarctation. The mRNA level of type I collagen pro-alpha2(I) was maximal at 3 days and returned to normal at 4 weeks. mRNA of pro-alpha2(I) was localized mainly in the outer media, adventitia and intima. Accumulation of type I collagen and its precursors was increased by 3 days, peaked at 4 weeks, and decreased toward normal by 8 weeks, corresponding to the distribution of pro-alpha2(I) mRNA. Gene expression for pro-alpha1(III) was similar to that of pro-alpha2(I) but was distributed throughout the media. We conclude that the mechanical stresses associated with an acutely induced alteration in pressure initiate rapid gene expression for collagen types I and III in the aortic wall. The response for collagen type I, predominantly in the outer media and adventitia, suggests that these regions play an immediate role in the resistance to excessive dilatation of the aorta. The diffuse response for collagen type III in the media suggests participation in a more extensive remodeling response associated with the reinforcement and reorganization of the musculo-elastic fascicles.

Abstract

Arterial diameter changes in response to flow. Chronic flow-mediated arterial enlargement may be mediated through metalloproteinase activity in the extracellular matrix of the arterial wall. We examined flow-mediated enlargement in the setting of increasing competitive matrix metalloproteinase (MMP) inhibition and with respect to gelatinase A and B expression and activity.Left common femoral arteriovenous fistulas (AVFs) were created in dose-response (52) and time course (34) cohorts of rats. Dose-response rats received either vehicle alone or 12.5, 25, or 37. 5 mg/kg b.i.d. RS 113,456, a competitive MMP inhibitor. Heart rate, blood pressure, and weight were measured at intervals following AVF construction. Aortic and common iliac diameters were measured on postoperative day (POD) 21. Untreated time course rats were sacrificed on PODs 0 (no AVF), 3, 7, 14, and 21. Aortic diameter was measured and the vessels were harvested for tissue analysis. Equal amounts of aortic RNA underwent reverse transcription and polymerase chain reaction with primers for MMP-2, MMP-9, and GAPDH. Zymography was performed on iliac artery tissue to measure gelatinolytic activity.A significant, stepwise reduction in flow-mediated aortic and left common iliac enlargement following left femoral AVF creation was noted with progressively higher doses of RS 113,456 without apparent hemodynamic or toxic effects. Right common iliac diameter was unchanged. Over 21 days following AVF creation, there was an upward trend in expression and activity for MMP-2 not evident for MMP-9.Flow-mediated arterial enlargement is limited by competitive MMP inhibition in a dose-dependent fashion. MMP-dependent flow-mediated enlargement may involve differential expression and activity of MMP-2 and MMP-9.

Abstract

Gaps in the internal elastic lamina (IEL) have been observed in arteries exposed to high blood flow. To characterize the nature and consequences of this change, blood flow was increased in the carotid arteries of 56 adult, male, Japanese white rabbits by creating an arteriovenous fistula between the common carotid artery and the external jugular vein. The common carotid artery proximal to the arteriovenous fistula was studied at intervals from 1 hour to 8 weeks after exposure to high flow. In the controls, the IEL showed only the usual, small, physiological holes, 2 to 10 microm in diameter. At 3 days, some of the holes in the IEL had become enlarged, but they could not be detected by scanning electron microscopy, despite manifest endothelial cell proliferation. At 4 days, gaps in the IEL appeared as small, luminal surface depressions, 15 to 50 microm wide. At 7 days, the gaps in the IEL had enlarged and formed circumferential, luminal depressions occupying 15+/-5% of the lumen surface. Endothelial cell proliferation persisted in the gaps while proliferative activity decreased where the IEL remained intact. At 4 weeks, as the artery became elongated and dilated, the gaps in the IEL widened as intercommunicating circumferential and longitudinal luminal depressions occupying 64+/-5% of the lumen surface. At 8 weeks, the rate of elongation and dilatation of the artery slowed and the widening of the gaps in the IEL diminished. Endothelial cells covered the gaps throughout. We conclude that flow-induced arterial dilatation is accompanied by an adaptive remodeling of the intima. The gaps in the IEL permit an increase in lumen surface area while endothelial cell proliferation assures a continuous cell lining throughout.

Abstract

To present novel techniques to prevent spinal ischemia during aneurysm creation and chronic bifurcated stent-graft implantation in an ovine model of abdominal aortic aneurysm (AAA).Experimental AAAs were created in 38 sheep. To prevent spinal ischemia, an internal aortic shunt was used during aneurysm creation. In the animals designated to receive bifurcated stent-grafts, a left external iliac-to-internal iliac bypass was performed to revascularize the caudal artery and prevent postdeployment spinal cord ischemia. Specimens were harvested at 1 week, 1, 3, and 6 months, and 1 year.Aneurysms were successfully created without paralysis in 35 animals. Two died due to aspiration pneumonia. Of the 33 animals implanted with endografts, 16 (94%) of 17 with straight devices and 15 (94%) of 16 with bifurcated stent-grafts survived with well-functioning, patent stent-grafts. Paralysis developed in 2 animals after endografting due to technical failures.The use of an internal shunt during aneurysm creation and internal iliac-to-external iliac transposition prior to bifurcated stent-graft deployment prevented spinal ischemia in an ovine AAA model. Chronically deployed stent-grafts were well tolerated.

Abstract

Patients with recurrent carotid artery stenosis are sometimes referred for carotid angioplasty and stenting because of reports that carotid reoperation has a higher complication rate than primary carotid endarterectomy. The purpose of this study was to determine whether a difference exists between outcomes of primary carotid endarterectomy and reoperative carotid surgery.Medical records were reviewed for all carotid operations performed from September 1993 through March 1998 by vascular surgery faculty at a single academic center. The results of primary carotid endarterectomy and operation for recurrent carotid stenosis were compared.A total of 390 operations were performed on 352 patients. Indications for primary carotid endarterectomy (n = 350) were asymptomatic high-grade stenosis in 42% of the cases, amaurosis fugax and transient ischemic symptoms in 35%, global symptoms in 14%, and previous stroke in 9%. Indications for reoperative carotid surgery (n = 40) were symptomatic recurrent lesions in 50% of the cases and progressive high-grade asymptomatic stenoses in 50%. The results of primary carotid endarterectomy were no postoperative deaths, an overall stroke rate of 1.1% (three postoperative strokes, one preoperative stroke after angiography), and no permanent cranial nerve deficits. The results of operations for recurrent carotid stenosis were no postoperative deaths, no postoperative strokes, and no permanent cranial nerve deficits. In the primary carotid endarterectomy group, the mean hospital length of stay was 2.6 +/- 1. 1 days and the mean hospital cost was $9700. In the reoperative group, the mean length of stay was 2.6 +/- 1.5 days and the mean cost was $13,700. The higher cost of redo surgery is accounted for by a higher preoperative cerebral angiography rate (90%) in redo cases as compared with primary endarterectomy (40%).In this series of 390 carotid operations, the procedure-related stroke/death rate was 0.8%. There were no differences between the stroke-death rates after primary carotid endarterectomy and operation for recurrent carotid stenosis. Operation for recurrent carotid stenosis is as safe and effective as primary carotid endarterectomy and should continue to be standard treatment.

Abstract

The beneficial effect of exercise in the retardation of the progression of cardiovascular disease is hypothesized to be caused, at least in part, by the elimination of adverse hemodynamic conditions, including flow recirculation and low wall shear stress. In vitro and in vivo investigations have provided qualitative and limited quantitative information on flow patterns in the abdominal aorta and on the effect of exercise on the elimination of adverse hemodynamic conditions. We used computational fluid mechanics methods to examine the effects of simulated exercise on hemodynamic conditions in an idealized model of the human abdominal aorta.A three-dimensional computer model of a healthy human abdominal aorta was created to simulate pulsatile aortic blood flow under conditions of rest and graded exercise. Flow velocity patterns and wall shear stress were computed in the lesion-prone infrarenal aorta, and the effects of exercise were determined.A recirculation zone was observed to form along the posterior wall of the aorta immediately distal to the renal vessels under resting conditions. Low time-averaged wall shear stress was present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. Shear stress temporal oscillations, as measured with an oscillatory shear index, were elevated in these regions. Under simulated light exercise conditions, a region of low wall shear stress and high oscillatory shear index remained along the posterior wall immediately distal to the renal arteries. Under simulated moderate exercise conditions, all the regions of low wall shear stress and high oscillatory shear index were eliminated.This numeric investigation provided detailed quantitative data on the effect of exercise on hemodynamic conditions in the abdominal aorta. Our results indicated that moderate levels of lower limb exercise are necessary to eliminate the flow reversal and regions of low wall shear stress in the abdominal aorta that exist under resting conditions. The lack of flow reversal and increased wall shear stress during exercise suggest a mechanism by which exercise may promote arterial health, namely with the elimination of adverse hemodynamic conditions.

Abstract

The results of a prospective, nonrandomized, multicenter clinical trial that compared endovascular stent graft exclusion of abdominal aortic aneurysms with open surgical repair are presented. During an 18-month period, 250 patients with infrarenal aneurysms underwent treatment at 12 study sites-190 patients underwent endovascular repair using the Medtronic AneuRx stent graft (Sunnyvale, Calif), and 60 underwent open surgical repair. There was no significant difference in operative mortality rates between the groups. The patients who underwent stent grafting had significant reductions in blood loss, time to extubation, and days in the intensive care unit and in the hospital, with an earlier return to function. The major morbidity rate was reduced from 23% in the surgery group to 12% (P

Abstract

The current paradigm for surgery planning for the treatment of cardiovascular disease relies exclusively on diagnostic imaging data to define the present state of the patient, empirical data to evaluate the efficacy of prior treatments for similar patients, and the judgement of the surgeon to decide on a preferred treatment. The individual variability and inherent complexity of human biological systems is such that diagnostic imaging and empirical data alone are insufficient to predict the outcome of a given treatment for an individual patient. We propose a new paradigm of predictive medicine in which the physician utilizes computational tools to construct and evaluate a combined anatomic/physiologic model to predict the outcome of alternative treatment plans for an individual patient. The predictive medicine paradigm is implemented in a software system developed for Simulation-Based Medical Planning. This system provides an integrated set of tools to test hypotheses regarding the effect of alternate treatment plans on blood flow in the cardiovascular system of an individual patient. It combines an Internet-based user interface developed using Java and VRML, image segmentation, geometric solid modeling, automatic finite element mesh generation, computational fluid dynamics, and scientific visualization techniques. This system is applied to the evaluation of alternate, patient-specific treatments for a case of lower extremity occlusive cardiovascular disease.

Abstract

The infrarenal abdominal aorta is particularly prone to atherosclerotic plaque formation while the thoracic aorta is relatively resistant. Localized differences in hemodynamic conditions, including differences in velocity profiles, wall shear stress, and recirculation zones have been implicated in the differential localization of disease in the infrarenal aorta. A comprehensive computational framework was developed, utilizing a stabilized, time accurate, finite element method, to solve the equations governing blood flow in a model of a normal human abdominal aorta under simulated rest, pulsatile, flow conditions. Flow patterns and wall shear stress were computed. A recirculation zone was observed to form along the posterior wall of the infrarenal aorta. Low time-averaged wall shear stress and high shear stress temporal oscillations, as measured by an oscillatory shear index, were present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. These regions were noted to coincide with a high probability-of-occurrence of sudanophilic lesions as reported by Cornhill et al. (Monogr. Atheroscler. 15:13-19, 1990). This numerical investigation provides detailed quantitative data on hemodynamic conditions in the abdominal aorta heretofore lacking in the study of the localization of atherosclerotic disease.

Abstract

Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved.Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume.Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl.This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

Abstract

To assess the effect of chronic, repetitive increases and decreases in blood flow on an artery.Arteriovenous fistulae were created in Japanese male rabbits between the left common carotid artery and the corresponding external jugular vein. Animals were placed into either control groups or one of six cycle groups consisting of flow variations (0.5 cycles, 1.0 cycle, 1.5 cycles, 2.0 cycles, 2.5 cycles and 3.0 cycles). Each complete cycle consisted of 4 weeks of increased flow followed by 6 weeks of normalised flow by fistula ligation.Arteries exposed to increased flow for 4 weeks (0.5 cycles) had a significant increase in lumen diameter without intimal thickening. After 6 weeks of normalised flow (1.0 cycle), shear stress became subnormal (0.42 +/- 0.17 N/m2), intimal thickening developed. In subsequent cycles, intimal thickening continued to develop with each point of flow normalisation and reduction in shear stress. Histologic and ultrastructural analysis revealed endothelial cells preservation at all time points, with individual strata of smooth muscle cell proliferation in the intima corresponding to the cycle numbers.Progressive intimal thickening occurred in the previously flow-induced remodelled artery when shear stress was reduced to subnormal levels with preserved endothelium, but was inhibited by high flow periods.

Abstract

We administered a specific, nonselective matrix metalloproteinase (MMP) inhibitor (RS-113,456) to examine the effect of MMP inhibition on flow-mediated arterial enlargement in a rodent arteriovenous fistula (AVF) model.Four groups of male Sprague-Dawley rats were created: sham (sham operated; n = 10), control (2.0 mm left common femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mL vehicle orally twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113,456 in 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arterial pressure, and body weight were recorded on postoperative days 0, 7, 14, and 21. On day 21, AVF patency was confirmed, the infrarenal aorta and common iliac arteries were exposed, blood flow velocity and external diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired, two-tailed Student t test, one-way analysis of variance, and the Bonferroni/Dunn procedure for post hoc testing.Heat rate, mean arterial pressure, and weight did not vary at any time between groups. Aortic and left iliac diameter was larger in the AVF groups than in sham groups (P < .001), and control and vehicle groups were larger than treatment groups (P < .0001). Changes in aortic and left iliac flow were also significant (AVF was more than sham and control, and vehicle was more than treatment). No difference in aortic and left iliac artery velocity and WSS or right iliac diameter, velocity, flow, or WSS was observed between groups.MMP inhibition diminishes flow-mediated arterial enlargement in the rat AVF model.

Abstract

Arteries enlarge in response to increased blood flow, but the molecular signals controlling this enlargement are not well understood. Basic fibroblast growth factor (bFGF) is a potent mitogen for endothelial cells (EC) and smooth muscle cells (SMC) and promotes cellular proliferation and differentiation. In order to determine whether bFGF is expressed in response to increased blood flow in vivo, carotid-jugular arteriovenous fistulas (AVF) were created in Japanese white rabbits. The carotid artery proximal to the fistula was harvested after 1, 3, or 7 days and compared to nonoperated, control carotid arteries. Arterial blood flow increased five- to eightfold in all AVF animals and resulted in a significant increase in wall shear stress. The proximal carotid artery arterial diameter was no different from control after 1 and 3 days (2.3 +/- 0. 1 mm) but enlarged to 2.9 +/- 0.1 mm (P < 0.05) after 7 days. RT-PCR revealed early transcription of bFGF mRNA at 1 and 3 days with increased densitometric band ratio (bFGF/beta-actin) at 7 days. Immunohistochemical analysis revealed bFGF protein localization in EC of control arteries as well as AVF arteries at all time points. SMC and adventitia expression of bFGF was absent in controls, minimal at 1 day, and increased after 3 and 7 days in the experimental groups. Western blotting confirmed the presence of bFGF in samples and transmission immunoelectron microscopy confirmed its nuclear localization. Endothelial cells in vivo express bFGF under both normal and elevated flow conditions. Smooth muscle cells, however, do not express bFGF under normal flow conditions but begin to express bFGF after 1 day of high flow with increased expression after 3 and 7 days. Flow-induced arterial enlargement begins after SMC expression of bFGF. Therefore, bFGF may play a role in arterial enlargement and adaptive remodeling in response to increased flow.

Abstract

The authors describe their experience with the use of single-piece, tapered stent-grafts for the treatment of abdominal aortic or aortoiliac aneurysms.Single-piece, tapered stent-grafts were placed in 15 patients for the treatment of abdominal aortic aneurysms with small distal necks (n = 13), and aortoiliac aneurysms (n = 2). There were 13 men and two women who ranged in age from 59 to 83 years (mean, 71 years). Usual open surgery was considered high risk in all patients because of comorbid medical conditions. The stent-grafts were made of Z stents covered with polytetrafluoroethylene (PTFE). Additional stent-grafts needed to treat perigraft leaks were made of Z stents covered with woven polyester (n = 5), Wallstents covered with PTFE (n = 2), Z stents covered with PTFE (n = 1), and a PTFE-covered Palmaz stent (n = 1). After stent-graft placement, the contralateral iliac artery was occluded by a blocking device composed of either a PTFE-covered Palmaz (n = 1) or Z stent (n = 13), and a femoral-femoral bypass was created.After placement of the stent-grafts, immediate perigraft leaks were observed in eight patients (53%). These were at the proximal (n = 5) or the distal end (n = 3). All, except one, were treated successfully with additional stent-grafts. The one failure was in a patient who developed aortic rupture after balloon dilation, requiring open surgical repair. Second procedures were required in four patients (27%), including three leaks treated successfully with coil embolization and/or a back-up stent-graft, and one stent-graft migration and thrombosis treated by thrombolysis and placement of an additional stent-graft. One patient died of respiratory failure 23 days after placement of the stent-graft. The mean follow-up was 12 months (range, 4-26 months). On the last follow-up, the aneurysms in the 13 living patients remained thrombosed.Treatment of aortoiliac aneurysms with use of single-piece, tapered stent-grafts is feasible in selected patients. The morbidity and mortality rates compare favorably with those of the open surgical procedures in a high-risk population. Further improvements in the technique and longer follow-up data are needed before this procedure can be recommended for the treatment of all aortoiliac aneurysms.

Abstract

Acute flow-induced arterial dilation is mediated by nitric oxide (NO). The role of NO in chronic flow-induced adaptive enlargement is unknown. We assessed the role of NO in arterial adaptation to increased blood flow (BF).Iliac artery BF was increased in adult male rats by creating a left femoral arteriovenous fistula. Left iliac BF and diameter were measured, and wall shear stress was calculated. The effect of the NO synthase inhibitor N omega-nitro-L-arginine-methyl ester (L-NAME) was studied in arteriovenous fistula rats divided into three groups (group 1, vehicle, group 2, 0.5 mg/ml; group 3, 2 mg/ml) in drinking water. Arterial diameter, blood pressure, and medial cell density were assessed after 21 days. Left iliac cyclic guanosine monophosphate content was measured in an additional group of animals.BF and wall shear stress in the left iliac artery increased fourfold immediately after arteriovenous fistula. Arterial enlargement was evident after 7 days, and wall shear stress normalized after 42 days. Flow-induced arterial enlargement was inhibited by both low- and high-dose L-NAME compared with control (analysis of variance p < 0.05). Blood pressure was elevated only in animals treated with high-dose L-NAME. Left iliac cyclic guanosine monophosphate content was lower in rats treated with L-NAME than in the control group (p < 0.05).NO suppression by L-NAME inhibits flow-induced iliac artery enlargement in rats. This finding suggests that NO plays a role in flow-induced arterial remodeling.

Abstract

Surgical treatment of abdominal aortic aneurysm (AAA) is being challenged by newer, minimally invasive therapies. Such new treatment strategies will need to prove themselves against concurrent results of standard operative AAA repair, within defined medical risk and aneurysm morphological categories. We review the natural history of AAAs, the medical risk levels for elective AAA repair, aneurysm morphology and its impact on operative mortality, the issue of high-risk patient treatment, and the current standard of care for AAAs based on single-center, multicenter, and population-based statistics. In good-risk patients, aneurysms > 5 cm in diameter are best treated by replacement with a prosthetic graft. Operative mortality should be < 5% 1-year survival > 90%. Aortic endograft techniques must meet or exceed these standards if they are to supplant standard surgical repair.

Abstract

The flow field inside a model of a polytetrafluorethylene (PTFE) canine artery end-to-side bypass graft was studied under steady flow conditions using laser-Doppler anemometry. The anatomically realistic in vitro model was constructed to incorporate the major geometric features of the in vivo canine anastomosis geometry, most notably a larger graft than host artery diameter. The velocity measurements at Reynolds number 208, based on the host artery diameter, show the flow field to be three dimensional in nature. The wall shear stress distribution, computed from the near-wall velocity gradients, reveals a relatively low wall shear stress region on the wall opposite to the graft near the stagnation point approximately one artery diameter in axial length at the midplane. This low wall shear stress region extends to the sidewalls, suture lines, and along the PTFE graft where its axial length at the midplane is more than two artery diameters. The velocity distribution inside the graft model presented here provides a data set well suited for validation of numerical solutions on a model of this type.

Abstract

To review the anatomic factors crucial to successful endoluminal abdominal aortic aneurysm (AAA) repair and propose an ideal endograft design for AAA exclusion.The anatomic features of critical importance to endovascular AAA exclusion comprise remote arterial access, proximal and distal fixation sites, AAA morphology, and arterial wall pathology. When designing an aortic endograft, the major components to consider are stent selection, graft material, and the delivery system. The ideal endograft design must be sufficiently versatile to treat a broad range of patients. To meet this requirement, the endograft should display a high degree of dimensional adaptability. A modular bifurcated endograft design permits intraoperative customization to tailor the device to each patient's anatomy and pathology.The modular stent-graft concept addresses many of the important factors in the evolution toward an ideal aortic endograft. Extensive testing will be needed to determine if the bifurcated stent-graft described here is the optimal design for effective AAA exclusion.

Abstract

In-vivo velocity profiles were recorded with a 20 MHz 80-channel pulsed Doppler ultrasound velocimeter in canine end-to-side ilio-femoral anastomotic grafts. The geometries were obtained from casts of the anastomotic region, and flow rates were measured with electromagnetic flow probes. Three cases reported here include a "standard" geometry, which was similar to previously studied in vitro models, a stenosed geometry, and a case with below average flow rate. Observed flow features include separation at the hood and toe, movement of the floor stagnation point, and skewed profiles in the proximal outflow segment. Out-of-plane curvature and lateral displacement of the anastomosis inlet appear to have a strong effect on the flow fields. In addition, compliance affects the instantaneous flow rates within the proximal and distal branches.

Abstract

Patients with aneurysmal disease involving both the descending thoracic and abdominal aorta have historically required simultaneous or sequential conventional operations, but the morbidity rate is high with either approach in these patients, who often exhibit coexisting cardiopulmonary disease. Transluminally placed endovascular grafts have recently been developed for repair of aortic aneurysms, and we have implemented these techniques to eliminate the need for a thoracotomy in patients with multilevel aortic disease.Since January 1994, 18 patients have undergone conventional abdominal aortic replacement with endovascular stent-graft placement into the descending thoracic aorta under fluoroscopic guidance through a 10 mm Dacron side limb off the abdominal graft. Abdominal aortic replacement required a tube graft in eight patients and bifurcated grafts in 10 patients. Thoracic stent-grafts (custom fabricated, woven Dacron covered, self-expandable stents) averaged 12.2 +/- 4.2 cm (mean +/- SD) in length.One patient died, resulting in a hospital mortality rate of 6%. No patients required further surgical intervention to treat their aortic disease. Seventeen patients (94%) are currently well 14 +/- 8 months after surgery (range, 3 to 29 months) with completely excluded thoracic aortic disease, no stent migration, and no change in stent configuration documented by serial radiologic examinations.Simultaneous abdominal aortic replacement and deployment of a thoracic stent-graft can safely exclude multilevel aortic aneurysmal disease and may be a valuable treatment option for these otherwise high-risk patients.

Abstract

Superior mesenteric blood flow in the fasting and postprandial state in humans can be measured accurately by cine phase-contrast (CPC) magnetic resonance (MR) imaging. Postprandial flow changes associated with mesenteric arterial occlusive disease (MAOD) are unknown.We used CPC MR imaging to measure fasting and postprandial blood flow in the superior mesenteric artery (SMA) and vein (SMV) in 22 patients (mean age, 69 years) with aortic occlusive disease and MAOD and compared the results with similar measurements in 8 younger, asymptomatic volunteers (mean age, 34 years). All 22 patients had stenosis or occlusion of the splanchnic or pelvic arteries demonstrated by contrast aortography; 19 were asymptomatic and 3 had symptoms of chronic mesenteric ischemia. Mean fasting blood flow was higher in patients (4.5 mL.kg-1.min-1) than in volunteers (2.3 mL.kg-1.min-1; P < .01). However, postprandial hyperemia (mean percentage change in SMV blood flow) was less in the asymptomatic (70%; P < .001) and symptomatic patients (29%; P < .01) than in the volunteers. Postprandial SMV flow was similar to SMA flow in the patients but was significantly greater than SMA flow in the volunteers (P < .005).Postprandial mesenteric hyperemia is reduced in older patients with MAOD. The role of aging alone has not been determined. Fasting and postprandial flow changes in these patients may predict the onset of chronic mesenteric ischemia.

Abstract

Conventional repair of aneurysms of the descending thoracic aorta entails thoracotomy and graft interposition. For elderly patients and those with previous operations, obesity, respiratory insufficiency, or other comorbidities, such a procedure entails significant mortality and morbidity. Transluminal stent-graft placement offers an alternative approach with potentially less morbidity and quicker recovery; however, the effectiveness and durability of stent-grafts remain uncertain.Since July 1992, thoracic aortic stent-grafts have been placed in 44 patients with a variety of pathologic conditions. Each graft was individually constructed from self- expanding, stainless-steel Z stents covered with a woven Dacron polyester fabric graft. Craft dimensions were determined from spiral computed tomographic scans. All implants were performed in the operating theater under fluoroscopic and transesophageal echocardiographic guidance. Follow-up was by computed tomography and contrast angiography in all cases. PATIENT DATA: There were 36 men and 8 women. Mean age was 66 years (range 35 to 88 years). Mean aneurysmal diameter was 6.3 cm (range 4.0 to 9.4 cm). Etiologies included 23 degenerative aneurysms, four posttraumatic aneurysms, four pseudoaneurysms, and one chronic aortic dissection.There were three early deaths (<30 days) and two late deaths. One early death resulted from graft failure. There were two instances of paraparesis or paraplegia, with one associated early death. A single stent was deployed in 27 patients, two stents were required in 14 patients, and three stents were required in three patients. In 23 patients, vascular access was attained through the femoral artery; abdominal aortic access, either native or graft, was necessary in the remaining 21 patients. Twelve grafts were placed in conjunction with open abdominal aortic surgical procedures. Mean follow-up (98% complete) was 12.6 months (range 1 to 34 months). One late death occurred from aneurysmal expansion and rupture in a patient with a persistent midgraft leak. The second late death may have resulted from aneurysmal rupture. Immediate thrombosis was achieved in 36 patients, and late thrombosis was achieved in three others. Failure to achieve complete aneurysmal thrombosis occurred in five patients, however, and one individual (previously noted) died of aneurysmal expansion and rupture; the remaining four are being carefully monitored. Only one patient has required conversion of the stent to an open procedure; a contained rupture of the false lumen of a chronic dissection eventually necessitated total descending thoracic aortic exclusion.These early results support the hypothesis that endovascular stent-graft placement may be a safe and durable treatment for selected patients with aneurysmal disease of the descending thoracic aorta. Large introducer size (26F outer diameter) and relatively limited angulation capability, as well as imprecise deployment techniques, currently limit its applicability. Distal embolization and stent migration have not been observed. Failure to achieve complete aneurysmal thrombosis may allow continued aneurysmal expansion and rupture. Further follow-up is clearly necessary to evaluate the true long-term effectiveness of this procedure.

Abstract

To evaluate the incidence and etiology of perioperative complications of carotid endarterectomy.Retrospective review of carotid endarterectomies performed over 13 years. Risk factors, indications, results of electroencephalographic (EEG) monitoring, and outcomes were evaluated.University medical center.Three hundred sixty-seven consecutive primary carotid endarterectomies were performed on 336 patients. Indications for operation included transient ischemic attack (48.5%), asymptomatic stenosis (24%), stroke (17%), nonlateralizing ischemia (9.5%), and stroke-in-evolution (1%).Postoperative neurologic deficits (permanent and transient) and deaths were correlated with preoperative symptoms, probable mechanism of the neurologic event, intraoperative EEG changes, and the use of intraoperative shunts.Four new permanent neurologic deficits (1.1%) and one transient postoperative deficit were noted. Of the five deficits, three were related to undiagnosed intraoperative cerebral ischemia and two were related to perioperative emboli. Three perioperative deaths (0.8%) occurred: two of myocardial infarction and one of an intracerebral hemorrhage from a ruptured arteriovenous malformation. Intraoperative EEG tracings for the most recent consecutive 175 procedures were analyzed. Shunts were used in 45 patients (26%), 38 of whom demonstrated significant EEG changes with carotid clamping.Carotid endarterectomy can be performed with a low risk of stroke (1.1%) and death (0.8%). Stroke was due to cerebral ischemia or embolization. With meticulous surgical technique, death is due to myocardial ischemia and not neurologic events.

Abstract

Many surgeons advocate uniform performance of operative completion arteriography after leg bypass surgery to ensure technical success and to optimize short- and intermediate-term graft patency. To determine the impact of this practice on the outcome of reversed-vein bypass surgery and associated patient charges, we reviewed our series of consecutive nonemergent leg bypass procedures. Ninety-three infrainguinal bypass procedures were performed in 80 patients (76 men and 4 women) from September 1991 to August 1994. The patients' average age was 67 years (range, 30 to 92 years). Follow-up (mean, 113.1 months; range, 1 to 36 months) was available on 91 grafts (97%). Indications for surgery included limb salvage in 75 cases, claudication in 12 cases, and popliteal aneurysm exclusion in 6 cases. All patients survived surgery. Primary graft patency rates as determined by life-table analysis were 87%, 81%, 78%, and 78% at 6 months and at 1, 2, and 3 years, respectively. Limb-salvage rates were 95%, 91%, 87% and 87% at the same intervals. Bypass procedures were divided into two groups. The 25 grafts in group 1 were evaluated with inspection, continuous-wave Doppler insonation, and routine completion arteriography. The 68 grafts in group 2 were evaluated by inspection and insonation alone. Fourteen grafts occluded after surgery (average, 5 months; range, 1 to 12 months), five in group 1 and nine in group 2. The likelihood of graft occlusion was similar in both groups (p = 0.42). The optimal method of confirming technical adequacy after bypass surgery in the clinically satisfactory graft remains uncertain. Charges for completion arteriography at our institution average $700, including 15 minutes of additional operative time. In our experience, these charges do not appear to be justified by improved short- or intermediate-term graft patency rates in reversed-vein grafts when completion arteriography is performed.

Abstract

Hypertension is a known clinical risk factor for atherosclerosis. In experimental atherosclerosis, monocyte adhesion to the endothelial surface is enhanced and is considered to be an important early stage in plaque formation. We tested the hypothesis that hypertension enhances monocyte adhesion in experimental atherosclerosis.Twenty-two New Zealand White rabbits were fed an atherogenic diet for 3 weeks to induce plaque formation. Aortic coarctation was created in eight rabbits by wrapping a Dacron band around the midportion of the descending thoracic aorta (stenosis group), whereas six rabbits underwent banding without aortic constriction (no stenosis group). Eight rabbits served as nonoperated controls. Monocyte binding to the aortic endothelial surface was counted with epifluorescent microscopy on standard aortic segments proximal and distal to the band. Immunohistochemistry was performed for the following antibodies: VCAM-1, RAM11, CD11b, and factor VIII.Mean blood pressure was 89 +/- 3 mm Hg in the aorta proximal to the stenosis, compared with 64 +/- 4 mm Hg in the no stenosis group and 74 +/- 3 mm Hg in the control group (p < 0.01). The mean aortic blood pressure gradient across the stenosis was 16 +/- 2 mm Hg in the stenosis group, whereas the aortic blood pressure gradient was 0.2 +/- 0.6 mm Hg in the no stenosis group and -0.3 +/- 0.4 mm Hg in the control group (p < 0.001). Monocyte adhesion to the aortic endothelial surface proximal to the stenosis was increased twofold compared with adhesion to the aorta distal to the stenosis and compared with the proximal aorta in the control group (p < 0.02). The proximal-to-distal aortic ratio of monocyte binding was enhanced in the stenosis group (2.2) compared with the no stenosis (0.76) and control (0.83) groups (p < 0.01). The intima area of the aorta proximal to the stenosis was significantly increased compared with the proximal aortas in the no stenosis and control groups (p < 0.01). RAM11, CD11b, and endothelial VCAM-1 expression were enhanced in the hypertensive region proximal to the stenosis.In the hypertensive region in the aorta proximal to the stenosis, monocyte adhesion and endothelial VCAM-1 expression were increased, with intimal thickening and accumulation of macrophages. These findings suggest that hypertension may promote atherosclerotic plaque formation by enhancing monocyte adhesion.

Abstract

Carotid endarterectomy has been firmly established as the gold standard of therapy for symptomatic and asymptomatic patients with severe carotid stenosis, provided surgical complication rates are within prescribed limits. The procedure-related risk of stroke/death should be < 3% in asymptomatic patients and < 6% in symptomatic patients. New investigational therapies such as balloon angioplasty and stenting for carotid stenosis should be evaluated against the same standard.

Abstract

The purpose of this study was to evaluate the incidence of thrombotic complications in patients with deep vein thrombosis (DVT) who were treated with percutaneous inferior vena caval interruption in place of anticoagulation.A retrospective review of all percutaneously placed inferior vena cava filters for 1 year, August 1993 through July 1994, was performed.Thirty-three percutaneous inferior vena cava filters were placed in 32 patients. The underlying disease was pulmonary embolism in 15 (47%) and DVT in 17 (53%) patients. Of patients with pulmonary embolism, 11 had a documented DVT, and four were not evaluated for DVT. There were 14 men and 18 women, with a mean age of 63.5 years (range 24 to 93 years). Indications for vena caval interruption were recurrent pulmonary embolism with therapeutic anticoagulation (n = 2 [6%]), prophylactic insertion with documented pulmonary embolism and therapeutic anticoagulation (n = 8 [25%]), documented pulmonary embolism and absolute contraindication to anticoagulation (n = 5 [16%]), documented DVT and absolute contraindication to anticoagulation (n = 2 [6%]), prophylactic insertion with documented DVT and therapeutic anticoagulation (n = 5 [16%]), and documented DVT with relative contraindication to anticoagulation (n = 10 [31%]). Of the 32 patients with inferior vena cava filters, 17 were not given anticoagulants (7 absolute contraindications, 10 relative contraindications), and 15 were given anticoagulants. Insertion of a percutaneous inferior vena cava filter in patients who were not given anticoagulants was followed by the development of phlegmasia cerulea dolens in four patients (24%), which was bilateral in two patients; one patient eventually died. No patients treated with inferior vena cava filter and anticoagulation had development of phlegmasia.Percutaneous inferior vena caval interruption effectively prevents pulmonary embolism in patients with DVT but does not impact the underlying thrombotic process and in fact may contribute to progressive thrombosis in patients who are not given anticoagulants. Anticoagulation with intravenous heparin in safe and effective therapy for DVT in most patients. We believe that percutaneous insertion of vena cava filters should not replace anticoagulation in routine proximal DVT, and those patients who require an inferior vena cava filter for failure of anticoagulation should continue to receive heparin to treat the primary thrombotic process. We caution that relative contraindications to anticoagulation should be carefully scrutinized before recommending vena cava interruption as a primary therapy for DVT.

Abstract

Magnetic resonance (MR) angiography and spiral CT angiography are promising new imaging modalities for evaluating patients with lower extremity arterial occlusive disease. Both techniques are less invasive than conventional angiography, and MR angiography has the additional advantages of not requiring iodinated contrast media or ionizing radiation. The basic principles of MR angiography and spiral CT angiography are reviewed with an emphasis on three-dimensional display techniques. This is followed by a discussion of their clinical applicability toward the diagnosis and treatment planning of lower extremity arterial occlusive disease.

Abstract

The artery wall adapts to changes in wall tension and wall shear stress by means of enlargement and changes in both thickness and composition. The intima may participate in these changes, and these compensatory adaptive-reactive modifications continue in the presence of atherogenesis. Further understanding of the interaction of the evolving plaque with the artery wall and the associated effects of the physical forces associated with the circulation should provide new insights into the nature of plaque instability and into the outcome of direct interventions.

Abstract

An automated three-dimensional particle tracking technique has been developed to study particle motion in modeled flow fields. A high speed video recording system. Kodak Ektapro 1000, with two cameras arranged relatively orthogonally is used for this technique. The particle tracking data are compared to theoretical Poiseuille flow and to laser Doppler data from an axisymmetric stenosis model. The particle tracking data are in good agreement with both theoretical and laser Doppler data, and at least 79 percent of the particle paths were determined successfully. Fluid dynamic properties derived by this technique are: 3-D particle paths, velocity, and particle residence time.

Abstract

Clinically significant atherosclerosis in the human aorta is most common in the infrarenal segment. This study was initiated to test the hypothesis that flowfield properties are closely related to the localization of plaques in this segment of the arterial system. Wall shear stress was calculated from magnetic resonance velocity measurements of pulsatile flow in an anatomically accurate model of the human abdominal aorta. The wall shear stress values were compared with intimal thickening from 15 post-mortem aortas measured by quantitative morphometry of histological cross sections obtained at standard locations. Wall shear stress oscillated in direction throughout most of the infrarenal aorta, most prominently in the distal region. The time-averaged mean wall shear stress (-1.7 to 1.4 dyn/cm2) was lowest near the posterior wall in this region. These hemodynamic parameters coincided with the locations of maximal intimal thickening. Statistical correlation between oscillatory shear and intimal thickness yielded r = 0.79, P < 0.00001. Low mean shear stresses correlated nearly as well (r = -0.75, P < 0.00005). Comparison of our data with surface maps of Sudan Red staining and early lesions as reported by others revealed similar conclusions. In contrast, pulse and maximum shear stresses did not correlate with plaque localization as has been shown for other sites of selective involvement by atherosclerosis (r < 0.345). Simulated exercise conditions markedly changed the magnitude and pattern of wall shear stress in the distal abdominal aorta. These results demonstrate that in the infrarenal aorta, regions of low mean and oscillating wall shear stresses are predisposed to the development of plaque while regions of relatively high wall shear stress tend to be spared.

Abstract

Arteries enlarge where intimal plaques form, tending to preserve lumen cross sectional area but causing an increase in mural tangential tension due to the increase in radius. To characterize the compensatory enlargement process at the carotid bifurcation and to evaluate the possible contribution of intima thickening to mural tensile support during the enlarging process, we assessed the relationships among intimal thickening, artery size and estimated tensile stress at 9 sequential axial levels in 42 human carotid bifurcations obtained during post-mortem examinations of 36 adults with no clinical or anatomical evidence of cerebrovascular disease. Right and left bifurcations were available for 6 patients. The arteries were fixed under conditions of controlled pressure distention and histologic sections were prepared at 0.5 cm axial intervals. We determined vessel radius (r), intima thickness (IT), media thickness (MT), intima area (IA), lumen area (LuA) and the area encompassed by the internal elastic lamina (IELA), i.e. the lumen area if there were no intimal thickening. Although IT, IA and r were greatest in the proximal sinus region, there was a highly significant linear relationship between IA and IELA at each axial level; correlation coefficients ranged from 0.64 to 0.97 with P < 0.001 at each level. Stenosis (IA/IELA x 100) ranged from 10.8 +/- 8.0% at the common carotid level immediately proximal to the bifurcation angle to 22.3 +/- 17.9% at the level immediately distal to the angle, but LuA remained nearly constant at each level regardless of IA.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

The spatial distribution of intimal thickening was determined for each of 42 carotid bifurcations removed at autopsy from patients with no clinical or anatomic evidence of cerebrovascular disease. Both right and left specimens were available for six of the individuals. Each bifurcation was removed intact and included a 1.5-2.9-cm length of the common carotid artery and a 1.5-2.5-cm length of the internal carotid artery. The specimens were restored to in situ length, fixed under conditions of controlled-pressure perfusion at 100 mmHg, filled with a radio-opaque mixture, radiographed and sectioned at 0.5-cm intervals. Computer assisted contour tracing of projected images of histologic sections was used to determine intimal thickness, intimal cross sectional area and lumen area within each of eight equal 45 degrees polar sectors with 0 degree indexed at the flow divider, 90 degrees at the outside wall, 180 degrees opposite the flow divider and 270 degrees at the inner side wall. Intima occupied 0.9-42% of the area encompassed by the internal elastic lamina, i.e. the potential lumen area if no intimal thickening were present, but there was no lumen narrowing on lateral X-ray projections. Intimal thickening was eccentric at each level of section but the circumferential location of maximum intimal thickness (MIT) shifted in a continuous helix from level to level. At the common carotid artery level 1.0 cm proximal to the bifurcation, MIT tended to be at the flow-divider side at 15 +/- 59 degrees. Immediately proximal to the flow divider, MIT was at the lateral side wall. In the mid-sinus region of the internal carotid artery MIT was opposite the flow divider at 179 +/- 64 degrees. At the distal internal carotid just beyond the sinus, MIT was at the inner side wall. The distal internal carotid was minimally involved or free of intimal thickening. Comparison of right and left bifurcations revealed that the helical spatial distribution of MIT was in mirror-image symmetry for the two sides. The findings correspond closely with previous demonstrations of a helical flow pattern in the region of the bifurcation. Although locations of MIT just proximal and just distal to the bifurcation are similar and tend to be at the 'far wall', individual differences in the shifts of MIT with axial location should be taken into account when sites of interrogation by non-invasive clinical methods are selected for detection of intimal thickening.

Abstract

Human aortic atherosclerosis is predominantly localized to the infrarenal aorta where flow is bidirectional and wall shear stress oscillates. Similar flow patterns have been related to carotid atherosclerosis. The thoracic aorta is usually spared, where flow and shear stress are unidirectional. We hypothesized that because heart rate and systemic blood pressure modulate flow velocity and shear stress oscillation, both these hemodynamic forces may enhance aortoiliac atherogenesis.Eighteen male cynomolgus monkeys were fed an atherogenic diet for 6 months (mean serum cholesterol = 535 +/- 35 mg/dl). Heart rate was determined with 24-hour electrocardiographic telemetry at monthly intervals and blood pressure was measured by direct arterial cannulation. The product of mean heart rate and mean blood pressure was used to define hemodynamic stress for each animal. Atherosclerotic lesion formation at three standard thoracic aortic sites was quantitatively compared with lesion formation at five standard infrarenal aortoiliac locations with computer-assisted morphometry.There was significantly more plaque in the aortoiliac segment than in the thoracic aorta (12.4% +/- 9.0% vs. 6.4% +/- 4.5% area stenosis, p = 0.02). No correlation was found between the degree of serum lipid elevations and lesion formation in either aortic location. Mean heart rate was 113 +/- 18 beats/min (87 to 163 beats/min) and mean blood pressure was 85 +/- 19 mm/Hg (62 to 130 mm Hg). Heart rate and blood pressure alone were not significantly related to lesion formation. A significant correlation was, however, found between hemodynamic stress and maximum lesion thickness (r = 0.47, p < 0.05) in the aortoiliac region but not in the thoracic aorta (r = 0.19, p > 0.10).This study demonstrates that heart rate and blood pressure exert a mutually potentiating effect on aortoiliac atherosclerosis but not on thoracic aortic atherosclerosis. Regional differences in aortic atherosclerosis may therefore be attributable to the interaction between these hemodynamic forces and the local flow patterns specific to each aortic location. Additional investigation of these hemodynamic factors in relation to human aortic atherosclerosis is warranted.

Abstract

To investigate the role of a compliant wall to the near wall hemodynamic flowfield, two models of the carotid bifurcation were constructed. Both were of identical internal geometries, however, one was made of compliant material which produced approximately the same degree of wall motion as that occurring in vivo while the other one was rigid. The inner geometries were formed from the same mold so that the configurations are directly comparable. Each model was placed in a pulsatile flow system that produced a physiologic flow waveform. Velocity was measured with a single component Laser system and wall shear rate was estimated from near wall data. Wall motion in the compliant model was measured by a wall motion transducer and the maximum diameter change varied between 4-7 percent in the model with the greatest change at the axis intersection. The mean shear stress in the compliant model was observed to be smaller by about 30 percent at most locations. The variation in peak shear stress was greater and occasionally reached as much as 100 percent with the compliant model consistently having smaller positive and negative peaks. The separation point was seen to move further upstream in the compliant cast. The modified flowfield in the presence of a compliant wall can then be important in the hemodynamic theory of atherogenesis.

The role of fluid mechanics in the localization and detection of atherosclerosis.Journal of biomechanical engineeringGiddens, D. P., Zarins, C. K., Glagov, S.1993; 115 (4B): 588-594

Abstract

Fluid dynamics research over the past twenty years has contributed immensely to our knowledge of atherosclerosis. The ability to detect localized atherosclerotic plaques using noninvasive ultrasonic methods was advanced significantly by investigations into the nature and occurrence of velocity disturbances created by arterial stenoses, and diagnosis of carotid bifurcation disease using a combination of ultrasonic imaging and Doppler measurement of blood velocity is now quite routine. Since atherosclerotic plaques tend to be localized at sites of branching and artery curvature and since these locations would be expected to harbor complex flow patterns, investigators postulated that fluid dynamics might play an initiating role in atherogenesis. Several fluid dynamic variables were proposed as initiating factors. Investigations were undertaken during the 1980s in which fluid dynamic model experiments with physiologic geometries and flow conditions were employed to simulate arterial flows and in which morphometric mapping of intimal thickness was performed in human arteries. Correlations between fluid dynamic variables and intimal thickness revealed that atherosclerotic plaques tended to occur at sites of low and oscillating wall shear stress; and these observations were reinforced by studies in a monkey model of atherosclerosis. Concomitantly, it was realized that arteries adapt their diameters so as to maintain wall shear stress in a narrow range of values around 15 dynes/cm2, findings which were based both on observations of normal arteries and on animal studies in which flow rates were manipulated and arterial diameter adaptation was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Direct graft replacement with local debridement and prolonged administration of antibiotics was used in the treatment of six patients with mycotic thoracoabdominal aneurysms. The only early death occurred in a patient with systemic sepsis related to Staphylococcus aureus mycotic suprarenal aneurysm. Long-term survival of the remaining patients has been excellent: two patients died of unrelated causes at 5 and 6 years, respectively; one patient remains alive with known persistent infection at 5 years; and the remaining patients are alive with no evidence of infection at 1 1/2 and 10 years, respectively. Percutaneous aspiration of infected perigraft fluid with local instillation of antibiotics along with administration of intravenous antibiotics may provide palliation in selected patients with recurrent infections. In view of the magnitude of the problems associated with recurrent infection, life-time administration of antibiotics is recommended after in situ graft replacement of mycotic thoracoabdominal aneurysms.

Abstract

To determine why some vein grafts fail, we prospectively studied the relationship between the histologic condition of the greater saphenous vein (GSV) at the time of grafting and subsequent stenosis of the vein graft.Ninety-four remnant segments of GSVs were obtained at the time of infrainguinal bypass in 91 patients and were perfusion fixed before histologic and ultrastructural examination. All bypass grafts were evaluated clinically and by duplex ultrasonography at regular intervals from 1 to 30 months after operation. All 24 grafts that developed lesions that caused thrombosis (failed grafts) or flow reduction (failing grafts) underwent arteriography and appropriate operative or other interventional correction of the causative lesion.There was no significant difference in the incidence of coronary artery disease, kidney disease, hypertension, or history of smoking in patients with normally functioning and failed or failing grafts. Diabetes occurred with an increased frequency in failed or failing grafts (p = 0.056). At the time of their insertion, GSVs that subsequently developed significant lesions had thicker walls (0.72 +/- 0.33 mm) compared with normally functioning grafts (0.58 +/- 21 mm; p < 0.02). Most of this difference was related to a significantly thicker intima (0.27 +/- 0.17 vs 0.11 +/- 0.7 mm; p < 0.0001). Another significant finding was the presence of subendothelial spindle-shaped cells greater than five cell layers thick. This occurred more often in pregraft biopsies from grafts that developed significant lesions (70.4% vs 7.5%, p < 0.0001). Electron microscopic examination of these cells demonstrated a subpopulation of poorly differentiated cells with few fibers and many vesicles. Four of 24 (17%) failed or failing grafts had evidence of vein wall calcification at the time of vein grafting. This was seen in only one (1.4%) of 70 normally functioning grafts without lesions (p < 0.005).We conclude that GSVs with thick and calcified walls or hypercellular intima at the time of grafting are at increased risk of developing intragraft lesions that may lead to graft failure. Frequent duplex ultrasonography surveillance is particularly warranted for such high-risk grafts.

Abstract

Cynomolgus monkeys were fed an atherogenic diet for 6 months following surgically produced high-grade (n = 10) or mild (n = 16) mid-thoracic aortic coarctation. A diet-control (DC) group (n = 13) was fed the diet without coarctation. High-grade coarctation (HGC) resulted in 74.1% +/- 8.3% stenosis by aortography prior to sacrifice and was associated with systolic brachial blood pressures of 143.3 +/- 26.0 mmHg and gradients across the stenoses of 36.8 +/- 23.6 mmHg. Mild coarctation (MC) resulted in stenoses of 50.9% +/- 12.9%, brachial systolic pressures of 119.4 +/- 25.7 and gradients of 12.5 +/- 15.2 mm Hg (P < 0.01, P = 0.03 and P < 0.005, respectively, compared with HGC). When total plaque cross-sectional area exceeded 0.8 mm2, the entire arterial circumference was usually involved. HGC resulted in complete sparing or minimal plaque formation in sections distal to the stenoses compared with proximal sections (P < 0.001). There were no significant differences between MC and DC animals in plaque location or size. Matrix content increased with plaque area regardless of degree of stenosis or sampling level (P < 0.01), but lesions with more than 75% matrix content were more numerous in distal than in proximal sections despite their smaller size. The number of plaques with greater than 75% matrix content was increased proximal to HGC (P < 0.04). Thus, distal location and plaque size were independent determinants of plaque matrix content and matrix content was increased proximal to HGC regardless of plaque size. Attempts to evaluate effects of various regimens and interventions on plaque composition need to take location and plaque size, as well as blood pressure differences, into account.

Abstract

CT imaging of traumatic aortic rupture has been both advocated and disparaged in the current literature as a reliable diagnostic modality. In a retrospective review of blunt chest trauma patients at our institution evaluated by both thoracic CT and arteriography, we found a 17% false negative rate and a 39% false positive rate. Although we feel CT is not sufficiently sensitive at present to evaluate traumatic rupture of the aorta directly, it is an invaluable adjunctive imaging modality for stable blunt chest trauma patients with equivocal chest radiographs or arteriograms.

Abstract

Flow behavior in models of end-to-side vascular graft anastomoses was studied under steady and pulsatile flow conditions. Models were constructed to simulate geometries employed in experimental studies on intimal thickening in a canine model. Reynolds numbers, division of flow in the outflow tracts and the pulsatile waveform employed were taken from measurements obtained in the canine model. Flows in the scaled-up, transparent models were visualized with white, neutrally buoyant particles which were photographed under laser illumination and also recorded on video tape under bright incandescent light. Strong, three-dimensional helical patterns which formed in the anastomotic junction were prominent features of the flow fields. Regions of low wall shear, oscillatory wall shear and long particle residence time were identified from the flow visualization experiments. Comparisons with the limited qualitative data available on intimal thickening in vascular graft anastomoses suggest a relation between localization of vascular intimal thickening and those surfaces experiencing low shear and long particle residence time.

Abstract

Arteries adjust to alterations in wall shear stress or tensile stress by changes in diameter, wall thickness, structure and composition. The intima participates in these adaptive reactions, particularly when changes in mechanical stresses are imposed after physiologic stress levels have been established during growth. Decreased wall shear stress due to decreased flow, flow separation or complex flow patterns, or increases in tensile stress due to increases in pressure or radius stimulate non-atherosclerotic intimal proliferation. Intimal fibrocellular hypertrophy (IFH), in the form of compact fibrocellular layers resembling the media, stabilizes when the lumen diameter is reduced sufficiently or wall thickness is increased sufficiently to restore baseline wall shear or tensile stress. Reactive-adaptive intimal proliferation is not necessarily self-limiting and may continue in the form of intimal hyperplasia (IH) which is relatively matrix-free and poorly organized. If mural and intimal changes do not result in restoration of baseline wall shear and tensile stress, IH may proceed to further narrowing and stenosis. Identification of the cellular and molecular mechanisms which underly the responses which link flow to diameter, diameter and pressure to mural restructuring, and mural restructuring to intimal thickening should provide new insights into the nature of vessel adaptations in the absence or presence of atherogenesis.

Abstract

We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino-atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148 +/- 11 to 103 +/- 20 beats/min, p < 0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136 +/- 22 beats/min), animals were separated into a low-heart-rate (LHR) group (111 +/- 16 beats/min, n = 12) and a high-heart-rate (HHR) group (150 +/- 16 beats/min, n = 5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross-sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01 +/- 1.19 compared with 0.76 +/- 0.42 mm2 for lesion area [p < 0.02] and 30.7 +/- 4.4% compared with 15.2 +/- 7.3% for stenosis [p < 0.002]).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

The infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta.

Abstract

We reviewed the structural basis of the mechanical properties of the arterial wall, in order to establish a coherent micro-anatomical basis for the differences in compliance among different arteries and a framework for assessing changes in the mechanical properties of specific individual arteries in relation to changing physical stresses.The data and concepts presented here were derived from both earlier and ongoing work. Features that assure stability and integrity in relation to blood flow (wall shear stress) and pressure (mural tensile stress) were examined. Particular attention was paid to the morphogenetic and biosynthetic means by which arteries adapt to normal or abnormal modifications of these forces, particularly in relation to growth, location in the arterial tree and geometric configuration.Thickness, composition and architecture of the artery wall, including thickness and composition of the intima, are normally determined by the stresses imposed by pressure and flow. Vessel radius is closely associated with flow, so that a normal baseline level of mean shear stress of about 15 dyn/cm2 is maintained or restored. Wall thickness and composition are determined by wall tension in relation to pressure and radius. Baseline levels of tensile stress differ with location but appear to be similar for homologous vessels. Changes in flow that modify the radius also modify wall tension. Changes in wall thickness and composition are likely to cause changes in compliance, due to altered flow and/or pressure patterns; these changes in compliance may be adaptive rather than destructive. Changes in the compliance of specific arteries over time may be used to evaluate the progression and severity of the conditions underlying these changes.

Abstract

All anastomotic intimal thickening may not be the same, and the underlying mechanism(s) regulating the different types may vary. We investigated the localization of experimental anastomotic intimal thickening in relation to known biomechanical and hemodynamic factors. Bilateral iliofemoral saphenous vein and polytetrafluoroethylene grafts were implanted in 13 mongrel dogs. The distal end-to-side anastomotic geometry was standardized, and the flow parameters were measured. After 8 weeks, seven of 10 animals (group I) with patent grafts were killed and the anastomoses fixed by perfusion. Histologic sections from each anastomosis were studied with light microscopy, and regions of intimal thickening were identified and quantitated with use of oculomicrometry. To characterize the anastomotic flow patterns, transparent silicone models were constructed from castings of the distal anastomosis of three animals (group II), and flow was visualized with use of helium-neon laser-illuminated particles under conditions simulating the in vivo pulsatile flow parameters. Histologic sections revealed two separate and distinct regions of anastomotic intimal thickening. The first, suture line intimal thickening, was greater in polytetrafluoroethylene anastomoses (0.35 +/- 0.23 microns) than in vein anastomoses (0.15 +/- 0.03 microns, p less than 0.05). The second distinct type of intimal thickening developed on the arterial floor and was the same in polytetrafluoroethylene (0.11 +/- 0.11 microns) and vein anastomoses (0.12 +/- 0.03 microns). Model flow visualization studies revealed a flow stagnation point along the arterial floor resulting in a region of low and oscillating shear where the second type of intimal thickening developed. High shear and short particle residence time were observed along the hood of the graft, an area devoid of intimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Autologous saphenous veins are considered the best arterial substitute for lower extremity revascularization in infected fields. The search continues for a vascular conduit in instances when an autologous biologic grafting is not feasible. Herein we report our experience with eight patients in whom cryopreserved saphenous vein allogenic homografts were used in 10 lower extremity arterial reconstructions for limb salvage with coexisting infection. Six patients with eight prosthetic grafts including four femoropopliteal, two femorotibial, a femorofemoral, and a femoroperoneal graft required complete or partial graft excision as a result of overt infection. The two remaining patients included one with an infected femoral pseudoaneurysm and another with extensive chemical burns. All cryopreserved saphenous vein allogenic homografts were of identical match to the ABO/Rh blood groupings of the recipient patients. No immunosuppressive drugs were administered after operation. Mean follow-up was 9.5 months (range, 6.0 to 14.0 months). One patient died 5 weeks after operation with a patent graft. Two grafts occluded during follow-up; in one graft, patency was restored with thrombectomy alone. The remaining seven arterial reconstructions continue to be patent with no evidence of aneurysmal dilation with complete eradication of the primary infection. These preliminary findings suggest that cryopreserved saphenous vein allogenic homografts can serve as interim conduits for lower extremity arterial reconstruction to preserve limb viability when autogenous conduits are unsatisfactory or unavailable. Further definitive reconstruction may thereafter be necessary once sepsis is eradicated and sufficient wound healing is achieved.

ANEURYSMAL ENLARGEMENT OF THE AORTA DURING REGRESSION OF EXPERIMENTAL ATHEROSCLEROSIS39TH SCIENTIFIC MEETING OF THE NORTH AMERICAN CHAPTER OF THE INTERNATIONAL SOC FOR CARDIOVASCULAR SURGERYZarins, C. K., Xu, C. P., Glagov, S.MOSBY-YEAR BOOK INC.1992: 90–101

Abstract

We explored the relationship between regression of diet-induced atherosclerosis and aneurysmal enlargement of the aorta in cynomolgus monkeys. Atherosclerotic plaques were induced in 17 monkeys by feeding them a diet containing 2% cholesterol and 25% peanut oil for 6 months (group I, n = 6; group III, n = 6) or 12 months (group II, n = 5). Regression was induced in group III by feeding a regression diet consisting of 0.25% cholesterol and 15% corn oil in a standard chow diet, for 6 months after the 6-month induction period. Serum cholesterol was 788 +/- 80 mg/dl after 6 months of induction, 508 +/- 53 mg/dl after the 12-month induction period, and 198 +/- 15 mg/dl in the regression group at 12 months. Aortas were fixed in situ under conditions of controlled pressure perfusion, and transverse sections of the unopened vessels were taken at standard levels in the midthoracic and abdominal aortic segments. The area encompassed by the internal elastic lamina was taken as a measure of artery size. Plaques were abundant in abdominal and thoracic sections after the 6- and 12-month induction periods, and no significant difference was observed in lumen area or artery size between the groups. The ratio of abdominal to thoracic aortic plaque area was markedly reduced in the regression group (0.3 +/- 0.2 for regression compared with 0.6 +/- 0.3 for 6-month induction and 1.3 +/- 0.2 for 12-month induction animals; p less than 0.05 for both). A twofold increase was observed in abdominal aortic lumen area in the regression group (10.0 +/- 1.5 mm2 for regression compared with 5.6 +/- 0.7 mm2 for the 6-month and 4.2 +/- 0.7 mm2 for the 12-month induction groups; p less than 0.05 for both) as well as a twofold increase in internal elastic lamina area (10.5 +/- 1.5 mm2 compared with 6.0 +/- 0.7 mm2 for the 6-month and 5.9 +/- 0.8 mm2 for the 12-month induction group; p less than 0.05 for both). Aortic enlargement in the regression group was accompanied by a reduction in media thickness in the abdominal aorta. No significant vessel enlargement or alteration in media thickness occurred in the thoracic aorta. One of six regression animals (17%) had a threefold enlargement of the abdominal aorta and was thought to have a manifest aneurysm.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract

Hypercholesterolemia and thrombosis have been implicated as factors in the development of atherosclerosis. Fibrinopeptide B (FPB) is a short chain peptide cleaved from fibrinogen during the production of fibrin. FPB is a known chemoattractant and has been shown to produce experimental atherosclerotic lesions in association with hypercholesterolemia. The present study was designed to examine the role of hypercholesterolemia in this process and to study the time course of the development of these lesions. Twelve New Zealand White rabbits were placed on an atherogenic diet and had suture carrying either FPB, fibrinopeptide A (FPA), or saline (controls) implanted in the adventitia of the femoral arteries and were sacrificed at 14 days. An equal number of animals were left on a standard diet and underwent similar treatment. Eleven animals were treated as the hypercholesterolemic group but were sacrificed at 2, 4, and 7 days. The thickness of the intima was measured adjacent to the suture in the animals sacrificed at 14 days, and the hypercholesterolemic FPB sites were thicker (12.23 mu +/- 6.60) than either hypercholesterolemic FPA (6.06 mu +/- 3.72), saline (4.94 mu +/- 1.42), or the normocholesterolemic FPB (5.99 mu +/- 4.61), FPA (3.89 mu +/- 2.20), or saline (3.97 mu +/- 1.83) (P less than 0.05 for all groups). Transmission electron microscopy of the hypercholesterolemic FPB group showed evidence of macrophages, actively secreting smooth muscle cells with newly deposited elastin, and foam cells by 7 days. We conclude that FPB attracts or stimulates macrophages and smooth muscle cells and that the resultant cellular and extracellular proliferation favors early atherosclerotic lesion formation in the presence of hypercholesterolemia.

Abstract

Vascular reconstruction for chronic intestinal ischemia can be accomplished by endarterectomy or aortomesenteric bypass. In our practice, antegrade bypasses from the supraceliac aorta to the celiac axis and superior mesenteric artery are currently the most frequently used techniques. Such reconstructions often use multiple or bifurcated large diameter vascular prostheses and have demonstrated excellent long-term patency. Despite these salutory results, we have noted an unusual perioperative response in three of these patients, which is the subject of this report. All three patients underwent uncomplicated elective mesenteric revascularization with grafts (diameter greater than or equal to 6 mm) originating in the supraceliac aorta. Indications for operation included (1) history of postprandial pain, (2) documentation of weight loss, and (3) angiographic evidence of advanced atherosclerotic disease with appropriate collateral development. Episodes of abdominal pain occurred 5 to 20 days after operation when normal food intake was reinstituted. In two patients immediate angiograms revealed patent grafts with diffuse mesenteric vasospasm. Treatment with intravenous hyperalimentation and nifedipine for 10 days resulted in complete resolution of symptoms. In the third patient, symptoms were totally relieved by temporary reduction in oral intake and administration of nifedipine. A later angiogram revealed a patent graft. All patients have remained asymptomatic and regained normal weight. This pattern of postrevascularization pain has not been seen in our patients undergoing revascularization with small (i.e., venous) conduits originating in the infrarenal aorta. The cause appears to be a heightened myogenic response of a "protected" vascular bed when suddenly exposed to the high perfusion pressure and blood flow of large caliber antegrade conduits. Prophylaxis with calcium channel blockers and use of smaller diameter grafts (5 mm) may avoid this disturbing syndrome.

Abstract

To assess the effect of hypertension on diet-induced coronary artery plaques after a return to a nonatherogenic diet, 10 cynomolgus monkeys were fed an induction regimen containing 2% cholesterol and 25% peanut oil for 6 months and then were subjected to midthoracic aortic coarctation to induce hypertension. The animals were then fed a nonatherogenic "prudent" ration for 6 additional months (hypertension-regression group). Twelve additional monkeys were fed the atherogenic diet for 6 months; six were killed (lesion-induction control group) and six were changed to the prudent diet for 6 additional months without coarctation (normotension-regression control group). At the end of the induction period, cholesterol levels averaged 744 +/- 178 mg/dl for the 22 animals and were similar for the three groups throughout the induction period. For the animals restored to the nonatherogenic diet (hypertension-regression and normotension-regression groups), serum cholesterol levels fell to 486 +/- 252 mg/dl at 1 month, to 341 +/- 162 mg/dl at 2 months, and to 234 +/- 78 mg/dl at 6 months. There was no significant difference between the hypertensive and normotensive animals. Six months after coarctation, blood pressure proximal to the coarctations for the hypertension-regression group ranged from 100/60 to 220/145 mm Hg with a mean of 166/103 +/- 36/28 mm Hg. Cross-sectional area of coronary plaques was somewhat lower for the normotension-regression control group compared with the lesion-induction control group, but the difference was not significant. Plaque area was, however, markedly greater in the hypertension-regression group than in either the lesion-induction or the normotension-regression groups (p less than 0.05 for each) despite progressive reduction in hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Ten patients with true aneurysmal disease of the hand and forearm vessels were treated at our institution between 1981 and 1990. Pseudoaneurysms resulting from penetrating trauma or mycotic aneurysms were specifically excluded. Eight patients were male, two were female; mean patient age was 38 years (range 26 to 72 years). A history of repetitive occupational or recreational trauma was elicited in five patients. All patients presented with painful masses or neurologic symptoms due to nerve compression. Ischemic changes were evident in five patients due to thrombosis or distal embolization. Arteriography and transcutaneous Doppler ultrasound aided in documentation of flow characteristics and planning for operative intervention. Three patients underwent excision and ligation once collateral flow was demonstrated to be adequate and reconstruction was not felt to be feasible. Seven patients underwent resection with vein graft reconstruction. Immediate postoperative and interval patency rates were 100%. No digital amputations were required even in those patients presenting with severe distal ischemia.

Abstract

If endothelial injury plays a prominent role in early atherogenesis, the plasma levels of von Willebrand factor (VWF), which is made within and normally released from endothelial cells, might be expected to rise as a marker of the cellular damage. To evaluate this hypothesis, we measured plasma VWF (as VIIIR:Ag), factor VIII:C, and serum lipids serially up to 37 weeks in 29 adult male cynomolgus monkeys on an atherogenic diet. Factor VIII:C peaked at 113% above baseline by week 10 (p less than 0.0001), then fell and remained 53% below baseline (p less than 0.04) during weeks 20 to 37. However, the overall rise in VWF was not significant. In contrast, serum cholesterol continued to rise after week 21. Serum phospholipids (PL), triglycerides (TG), and free fatty acids (FFA) showed a temporal pattern similar to VIII:C. Significant positive correlations with VIII:C were noted for PL (r = 0.59, p = 0.0001) and TG (r = 0.36, p = 0.0096). At autopsy, small to moderately advanced atherosclerotic lesions were distributed throughout the aortas of the majority of the animals. We conclude that changes in plasma VIIIR:Ag do not correlate with atherogenesis in this model. However, the similar course of VIII:C, TG, and PL suggests that these substances may be involved and perhaps interrelated early in atherogenesis.

Abstract

To determine whether aneurysms form in experimental diet-induced atherosclerosis, we reviewed our experience with cynomolgus monkeys (n = 268) and rhesus monkeys (n = 175) fed an atherogenic diet for various lengths of time. Many animals in long-term experiments were fed "regression" diets and cholestyramine to lower cholesterol levels after lesions were established. No aneurysms were found in animals on normal diet. There were no aneurysms in 252 animals fed an atherogenic diet with or without regression for 12 months or less. However, aneurysms formed in 13% of cynomolgus monkeys (4 of 31) and 1% (1 of 107) rhesus monkeys on an atherogenic regimen for 16 to 24 months. Four of the five animals with aneurysms were on a regression diet and cholestyramine for 4 to 12 months. The fifth was fed the atherogenic diet for 20 months without subsequent regression. Aneurysms were prominent and involved the thoracic and abdominal aorta, innominate artery, carotid arteries, iliac and femoral arteries, and formed in areas most involved with plaque formation in both species. Histologic evidence was found of thinning of the media and atrophy with loss of normal architecture. The higher incidence of aneurysms in cynomolgus monkeys was associated with greater media destruction than was noted in the rhesus. These data support the thesis that aneurysm formation is a manifestation of atherosclerosis. In primate atherosclerosis, aneurysms form only after prolonged exposure to the atherogenic regimen, even in the presence of declining serum cholesterol levels. Matrix fibers in plaques may provide structural support to the aortic wall where there is underlying atrophy of the media. With time or declining serum cholesterol levels or both, plaques may atrophy leaving an aortic wall too thin to support increasing mural tension, leading to aneurysmal enlargement.

Abstract

The development of atherosclerotic lesions involves many cell types, including macrophages. Fibrinopeptide B (FPB) has been shown to be a potent chemotactic agent for macrophages, which are abundant as intimal foam cells in atherosclerotic lesions, especially in cholesterol-fed rabbits. We hypothesize that intimal low-density lipoproteins also cause fibrinogen in the intima to release FPB and that FPB attracts macrophages in response to the high lipid levels associated with lesion development. To test our hypothesis, we used an atherosclerotic model. Silk sutures containing either FPB, fibrinopeptide A (FPA), lipopolysaccharide (LPS), or saline control were prepared. One suture of each type was placed in the adventitia of the femoral artery of a rabbit. Animals were killed at 1 or 2 weeks. Only vessels exposed to either FPB or LPS showed significant intimal thickening in the region adjacent to the suture site. Semi-thin electron microscopic sections indicated that the intimal wall was highly cellular and that many cells contained lipid vacuoles after 2 weeks. These sections also showed that the endothelium remained intact and that no injury to the media of the artery had occurred. Electron microscopy of the tissue samples showed the proliferation of smooth muscle cells and deposition of extracellular matrix in the 2-week animals, whereas foam cells were present in the 1-week animals. We conclude that FPB does indeed attract macrophages to the intima and that these macrophages may become foam cells. The model we have developed can be used to study possible mechanisms for the entry of macrophages into the intima during early lesion development and to further understand the complex interactions of FPB, fibrinogen, and lipids in atherosclerotic lesion development.

Abstract

To assess the extent to which endothelial cell (EC) structure is modified by hyperlipidemia and by the formation of intimal plaques, we undertook a quantitative ultrastructural study of aortic EC of cynomolgus monkeys after 3 or 6 months on an atherogenic diet. We compared EC in lesion-free areas (LFA) with EC overlying focal discrete foam cell accumulations (FDA) or covering multilayered confluent plaques (MCP). There was a 15% increase in cross-sectional lumen surface profile length over FDA or MCP compared to LFA (p less than 0.005) corresponding to the bulging contours of immediately underlying foam cells. There was, however, no increase in the number of EC per unit of surface area (26.2 +/- 4.47 per 10(4) mm2 for LFA and 26.0 +/- 4.22 for FDA) or, on cross-section, per 100 microns length of underlying internal elastic lamina (8.79 +/- 2.42 for LFA, 8.26 +/- 2.01 for MCP). Nor did the number of surrounding cells contacted by each cell over LFA or MCP differ from normolipemic controls (6.56 +/- 0.85 for LFA and 5.58 +/- 0.86 for MCP). Most ECs were markedly attenuated over lesions, and while the extent and complexity of lateral contact regions between adjacent EC was diminished, the number and complexity of basilar projections was greatly increased. These structures extended among the intimal foam cells to insert on the internal elastic lamina or on intimal matrix fibers, resulting in a 2.7-fold increase in the length of the abluminal portion of the EC profile. The perimeter of the transverse EC profiles was thereby increased from 41.4 +/- 2.12 microns in LFA to 82.2 +/- 5.21 microns over MCP (p less than 0.0001). Polarization of EC in the direction of flow diminished as lesions developed. The ratio of length to width, as well as the standard deviation of the ratio, decreased from 3.51 +/- 3.92 in LFA to 2.35 +/- 0.25 over MCP, due mainly to increases in the proportion of the cell perimeter exposed to the lumen. Lesion localization bore no relationship to the orientation of EC in corresponding locations in the normolipemic controls or in LFA immediately adjacent to plaques. Organelles of EC in hyperlipidemic animals showed features suggestive of increased metabolic activity in all regions, and stress filaments were increased in the EC attenuated over lesions. There was no evidence of EC degeneration, necrosis, or sloughing regardless of lesion location, size, or complexity.

Abstract

This retrospective study compared the results of percutaneous transluminal angioplasty (PTA) with those of infrainguinal bypass procedures in patients with critical arterial ischemia to determine which procedure had superior patency, limb salvage, and durability. The records of 54 patients who underwent 54 PTAs and 56 patients who underwent 63 infrainguinal bypasses (29 femoropopliteal and 34 femorodistal) from 1981 to 1987 were reviewed. In each patient PTA or bypass was the initial vascular procedure. Patients in both groups were comparable with respect to age, sex, and the presence of diabetes, hypertension, obesity, hypercholesterolemia, and smoking. Mean follow-up was 40 months (4 to 88 months) for the PTA group and 28 months (6 to 78 months) for the surgery group. Thirty-nine of the 54 patients (72%) were initially improved after PTA, whereas 15 patients (28%) showed no improvement. During follow-up, 20 initially successful PTAs reoccluded. Thirty-two of 54 patients (59%) underwent subsequent procedures, which included repeat PTA (10) and distal bypass (14). Patency determined by noninvasive Doppler studies was 18% at 2 years. Limb salvage, which included such secondary procedures, was 78%. Two-year patency for femoropopliteal bypasses was 68% with a limb salvage of 90%. Femorodistal bypasses had a 2-year patency of 47% and a limb salvage of 74%. No perioperative deaths occurred. Twenty-one of the 63 patients (33%) had subsequent procedures, which included thrombectomy (5) and bypass revision (9). In patients treated for limb-threatening ischemia the 2-year patency after femoropopliteal bypass (68%) or femorodistal bypass (47%) is significantly better than that from PTA (18%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

To identify microanatomic and chemical features that may mark the transition from asymptomatic to symptomatic atherosclerotic carotid lesions, we evaluated 62 carotid artery bifurcation plaques including 45 high-grade stenoses removed at endarterectomy and 17 nonstenotic plaques recovered at autopsy. Morphologic features were evaluated on multiple-interval histologic sections and were graded for the presence of hemorrhage, ulceration, thrombosis, lumen surface irregularity, and calcification. Plaque hemorrhage, recent and remote, was found in most of the specimens, and did not discriminate between symptomatic and asymptomatic stenotic plaques. High-grade carotid stenotic plaques were associated with a significantly higher incidence of ulceration (53%), thrombosis (49%), and lumen irregularity (78%) when compared to nonstenotic asymptomatic plaques (6%, 0%, and 17%, respectively; p less than 0.01). Although these features were more prominent in lesions that produced symptoms, they were present in 80% of the stenotic bifurcations, and did not distinguish between symptomatic and asymptomatic endarterectomy plaques. No significant differences were found between symptomatic and asymptomatic high-grade lesions with respect to collagen, DNA, total cholesterol, fibrinogen, lipase, elastase, or collagenase content. We conclude that intraplaque hemorrhage is commonly seen in carotid plaques even without severe stenosis, and it does not appear to be a dominant determinant of symptoms. Ulceration and surface thrombi that may lead to cerebral embolization are prominent features in markedly stenotic plaques even when symptoms are absent. The disruptive processes that underlie plaque instability appear to be closely associated with plaque size and stenosis rather than plaque composition.

Abstract

Specific hemodynamic factors have been shown to be associated with atherosclerotic plaque localization at the human carotid bifurcation. Flow field characteristics may also determine plaque distribution in the abdominal aorta. We therefore characterized flow patterns in a glass model abdominal aorta that included its major branches under conditions of steady flow. Outflow resistances of the celiac, superior mesenteric, renal, inferior mesenteric, and iliac arteries were varied to produce flow distributions consistent with rest, the postprandial state, and vigorous lower limb exercise. Flow patterns were visualized with three colors of dye injected simultaneously through capillary tubes at selected locations and recorded as still photographs and by cinephotography on videotapes. Under resting conditions a large region of flow separation and stagnation occurred at the posterior wall of the aorta directly opposite the orifices of the superior and inferior mesenteric arteries. Similar separation regions were observed during the simulated postprandial state but diminished markedly when distal outflow was increased to levels consistent with exercise. In the highly susceptible infrarenal aortic segment, beginning about 2 cm below the renal artery orifices, multiple secondary flow patterns with three to four counterrotating vortex formations were observed under both resting and postprandial conditions but disappeared in the exercise state. Secondary flow patterns were not noted in the suprarenal abdominal aorta, which is usually relatively spared. Such features have been related to plaque localization elsewhere, and the disappearance of these patterns with increased flow velocity during exercise is consistent with the previously noted protective effect of unidirectional laminar high-flow states. The beneficial effects of physical fitness programs may be related in part to these hemodynamic modifications.

Abstract

Arteries respond to long-term changes in flow rate by alterations in caliber that tend to restore wall shear stress to normal baseline levels. Changes in radius, pressure, or geometric configuration elicit changes in structure and composition of the media in keeping with the altered level and distribution of tensile stresses. Similar stabilizing adaptations occur in the presence of conditions that induce the formation of atherosclerotic plaques, but the ultimate effectiveness of these reactions is variable. Several recent experiments provide information on the possible effects of hyperlipidemia on the smooth muscle cell (SMC) response to normal or increased levels of mechanical stress: (a) Normolipemic serum increases collagen synthesis by SMCs grown on purified elastin membranes compared to synthesis in serum-free medium, but synthesis is not further enhanced by cyclic stretching of the cells. Collagen production increase is less marked in hyperlipemic serum, but cyclic stretching raises synthesis to a degree comparable to that noted for serum-free medium. (b) The increase in artery diameter in response to increased flow rate and the elaboration of media components in relation to the increase in diameter are not hampered by hyperlipidemia. (c) The compensatory enlargement of arteries in response to plaque formation is not prevented by hyperlipidemia even in the presence of hypertension. (d) The healing of a transmural necrotizing injury of the media is, however, retarded and incomplete in the presence of hyperlipidemia. These findings indicate that hyperlipidemia per se does not necessarily interfere with the SMC response to mechanical stimuli. The usual adaptive reactions remain intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

A case illustrating fracture and translocation of a Kim-Ray Greenfield filter strut due to intraoperative manipulation of the filter during cholecystectomy is presented. Awareness of this previously unreported complication is essential in preventing its occurrence.

Abstract

The evaluation of clinical reports on vascular disease is often made difficult by variations in descriptive terms, clinical classification, and outcome criteria. In 1983 the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery created the Ad Hoc Committee on Reporting Standards to address these problems and recommend solutions. Some general problems were addressed in the initial report dealing with lower extremity ischemia. This article concerns clinical standards for reports dealing with cerebrovascular disease, suggests a scheme for clinical classification, and recommends standardized reporting practices for grading risk factors, angiographic and other diagnostic findings, and the results and complications of therapeutic intervention.

Abstract

Atherosclerosis affects the major elastic and muscular arteries, but some vessels are largely spared while others may be markedly diseased. The carotid bifurcation, the coronary arteries, the infrarenal abdominal aorta, and the vessels supplying the lower extremities are at highest risk. The propensity for plaque formation at bifurcations, branchings, and curvatures has led to conjectures that local mechanical factors such as wall shear stress and mural tensile stress potentiate atherogenesis. Recent studies of the human vessels at high risk, and of corresponding models, have provided quantitative evidence that plaques tend to occur where flow velocity and shear stress are reduced and flow departs from a laminar, unidirectional pattern. Such flow characteristics tend to increase the residence time of circulating particles in susceptible regions while particles are cleared rapidly from regions of relatively high wall shear stress and laminar unidirectional flow. The flow patterns associated with plaque localization are most prominent during systole. Long-term consequences are therefore likely to be greatly enhanced by elevated heart rate and may exert a selective effect on the coronary arteries. The point-by-point redistribution of wall tension at regions of geometric transition has not been quantitatively related to plaque localization. Enlargement of arteries as plaques increase in size and the associated modeling of plaque and wall configuration tend to preserve an adequate and regular lumen cross section. Hemodynamic forces appear to determine changes in vessel diameter so as to restore normal levels of wall shear stress, while wall thickness architecture, and composition are closely related to tensile stress. Hemodynamic forces may also be implicated in the symptom-producing destabilization of plaques, especially in relation to wall instabilities near stenoses. The relative roles of wall shear stress, tensile stress, and the metabolism of the artery wall in the progression and complication of atherosclerosis remain to be clarified. Development of clinical techniques for relating hemodynamic and tensile properties to plaque location, stenosis, and composition should permit pathologists to provide new insights into the bases for the topographic and individual differences in plaque progression and outcome.

Abstract

We studied the relationships among intimal plaque area, lumen area, and artery size in 481 sections of the left anterior descending (LAD) coronary artery taken at four standard sampling sites in 125 pressure-perfusion-fixed postmortem adult human hearts. The internal elastic lamina area was considered to be a measure of artery size or potential lumen area. Artery size correlated strongly with intimal plaque area at each LAD level (p less than 0.0001). Stepwise regression analysis revealed that plaque area was the principal determinant of artery size at each LAD level (r2 = 0.20 to 0.33). Sections of arteries with the most intimal plaque (highest quartile) were compared with those with the least plaque (lowest quartile) at each sample site. In the proximal LAD artery, the most severely diseased arteries increased in size 62% but lumen area decreased 25%. In the midportion of the LAD artery, plaque area was 10 times greater in the most diseased arteries, but lumen area remained normal because of an 80% increase in artery size. In the most severely diseased distal LAD artery sections, despite a fourteenfold increase in plaque area, lumen area almost doubled because of a marked increase in artery size. If no enlargement had occurred, the most severely diseased arteries in the proximal LAD segment would have developed a 92% lumen stenosis rather than the observed 25% lumen stenosis. In the distal LAD artery, without enlargement there would have been a 65% lumen stenosis rather than the 85% increase in lumen area that was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

A flexible, rotating tip catheter (Kensey catheter) was used to recanalize 24 segments of diseased superficial femoral arteries (from cadavers) that were sewn as xenografts into the femoral, carotid, or aorticorenal arteries of 14 dogs. One perforation occurred; there were emboli in some brains and kidneys, the consequences of which remain unknown. No signs of gross neurologic deficits or limb ischemia were seen at 0-11 days.

Abstract

Saphenous vein resistance influences graft flow rates and may affect graft patency in lower limb revascularization. To quantitate specifically the contribution of saphenous vein valves to this resistance, 10 human saphenous veins (mean length 68 cm, diameter 0.42 mm, and 5.2 valves per vein) were perfused with water under carefully controlled pressure gradients designed to simulate different peripheral resistances in the outflow bed. The Reynolds number was maintained at 350 to 600, within the physiologic range for in vivo grafts. Veins were perfused under both venous (10 mm Hg) and arterial (100 mm Hg) mean pressures to determine the effects of distension on the overall resistance of the conduit. The valves were bisected according to Leather's techniques and flow was measured in both directions, antegrade (simulating "reversed" grafts) and retrograde (simulating "in situ" grafts). Data (mean +/- standard error) were normalized to the baseline flow for each vein with intact valves and expressed as a percentage change. Data were analyzed by means of Student's t test (p less than 0.05). Baseline antegrade flow with intact valves averaged 71.0 +/- 3.0 ml/min at pressure gradients (delta P) of 10 mm Hg and 95.0 +/- 2.6 ml/min for delta P = 20 mm Hg. After valve incision, antegrade flow (reversed) increased an average of 29% at both pressure gradients. Retrograde flow (in situ) through the bisected valves was only 19% greater than baseline antegrade flow and was significantly less than antegrade flow through bisected valves. The difference is explained by theoretic considerations of stenosis area and orifice shape. The increases in flow did not correlate with vein length or diameter, nor did flow change with different distension pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Whether human coronary arteries undergo compensatory enlargement in the presence of coronary disease has not been clarified. We studied histologic sections of the left main coronary artery in 136 hearts obtained at autopsy to determine whether atherosclerotic human coronary arteries enlarge in relation to plaque (lesion) area and to assess whether such enlargement preserves the cross-sectional area of the lumen. The area circumscribed by the internal elastic lamina (internal elastic lamina area) was taken as a measure of the area of the arterial lumen if no plaque had been present. The internal elastic lamina area correlated directly with the area of the lesion (r = 0.44, P less than 0.001), suggesting that coronary arteries enlarge as lesion area increases. Regression analysis yielded the following equation: Internal elastic lamina area = 9.26 + 0.88 (lesion area) + 0.026 (age) + 0.005 (heart weight). The correlation coefficient for the lesion area was significant (P less than 0.001), whereas the correlation coefficients for age and heart weight were not. The lumen area did not decrease in relation to the percentage of stenosis (lesion area/internal elastic lamina area X 100) for values between zero and 40 percent but did diminish markedly and in close relation to the percentage of stenosis for values above 40 percent (r = -0.73, P less than 0.001). We conclude that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area. The preservation of a nearly normal lumen cross-sectional area despite the presence of a large plaque should be taken into account in evaluating atherosclerotic disease with use of coronary angiography.

Abstract

We performed transluminal balloon angioplasty in 24 cadaver and nine amputated limb superficial femoral arteries under controlled experimental conditions. The cadaver arteries were excised, restored to in situ length, redistended, and maintained at 100 mm Hg intraluminal pressure at 37 degrees C throughout the angiographic and dilation procedure and during fixation. The amputated limb arteries were dilated and pressure perfusion-fixed after dilation. Quantitative analysis of cadaver vessels revealed that arteries with prominent atherosclerotic lesions had the same internal elastic lamina (IEL) circumference (15.6 +/- 1.0 mm) as those with little or no stenosis (16.8 +/- 0.5 mm) but lumen area (8.8 +/- 1.7 mm2) was markedly reduced compared to nonstenotic sites (20.0 +/- 1.9 mm2, p less than 0.01). Lesions occupied 49 +/- 6% of the area circumscribed by the IEL in cadaver arteries with prominent plaques. After dilatation, lumen areas at stenotic sites were enlarged 43% on histologic sections (12.6 +/- 1.8 mm2 vs 8.8 +/- 1.7 mm2, p less than 0.01) and 31% as determined by angiography (p less than 0.05) when compared to immediately adjacent nondilated regions. The increased lumen area was associated with splitting of the intima near the edges of the plaque, separation of the edges of the plaque from the media, and stretching of the media and adventitia, often with accompanying rupture of the media. There was no evidence of plaque compression, fragmentation, deformation, modeling, or herniation into the media. The detached wedge-shaped edges of the lesions formed flaps projecting into the lumen, resulting in a marked increase in lumen irregularity on cross-section.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Transesophageal echocardiography (TEE) was used to detect segmental ventricular wall motion abnormalities (SWMAs) associated with ischemia in 49 high-risk patients who had 50 major vascular procedures, including 23 infrarenal aortic, five suprarenal aortic, 14 carotid, seven distal, and one axillofemoral reconstructions. A modified gastroscope tipped with an echocardiographic transducer was inserted into the esophagus and positioned behind the heart to obtain a reproducible cross-sectional view of the left ventricle at the level of the papillary muscles. Twelve patients (24%) had SWMA at baseline, probably representing areas of old infarction. Fourteen patients (28%) had new intraoperative SWMAs. Ten of 14 patients were successfully treated and wall motion was normalized. One of the four patients with persistent SWMA suffered a nonfatal subendocardial infarct; another patient suffered intraoperative cardiac arrest and died. No infarcts were documented in the 10 patients successfully treated. The mortality rate in the entire high-risk group was 6%. Alterations in ventricular wall motion were noted in almost 50% of high-risk patients undergoing major vascular surgery. Seventy-one percent of acute SWMAs were reversed without any evidence of myocardial infarction. TEE allowed early recognition of evolving myocardial ischemia and facilitated immediate and specific fluid and pharamcologic interventions. Continued application of this technique may reduce the incidence and morbidity of perioperative cardiac complications.

Abstract

We studied the adaptive response of the arterial wall and intimal thickening under conditions of increased flow in an atherogenic model. Blood flow was increased by construction of an arteriovenous fistula between the right iliac artery and vein in six cynomolgus monkeys fed a diet containing 2% cholesterol and 25% peanut oil. The left iliac artery served as the control. Serum cholesterol increased from 135 +/- 22 mg/dl to 880 +/- 129 mg/dl during the experiment. After 6 months, blood flow in the right iliac artery (420 +/- 95 ml/min) was 10 times greater than in the left iliac artery (44 +/- 9 ml/min, p less than 0.005). Flow velocity in the right iliac artery (31 +/- 6 cm/sec) was more than twofold greater than in the left (12 +/- 1 cm/sec, p less than 0.05). Despite the marked difference in blood flow and flow velocity, calculated wall shear stress was the same in both the right (16 +/- 4 dynes/cm2) and left iliac vessels (15 +/- 2 dynes/cm2) because of a twofold increase in lumen diameter (p less than 0.001) of the right iliac artery. Shear stress in the aorta was also normal (12 +/- 2 dynes/cm2). There was no difference in plaque deposition or mean intimal thickness between the right and left iliac arteries. In the right iliac artery there was a twofold increase in media cross-sectional area (p less than 0.001) but no change in media thickness or total wall thickness. Tangential wall tension and tangential wall stress were two times greater on the right than on the left (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

We have studied mechanical factors that could determine how stenosis protects against distal atherosclerosis in cynomolgus monkeys fed an atherogenic diet. Critical aortic stenosis was produced by coarctation of the thoracic aorta. After 3 months, coarcted monkeys had a mean aortic pressure gradient of 25 +/- 1 mm Hg and a 76% +/- 2% lumen stenosis. Aortic wall motion was measured by means of in vivo ultrasonic sonomicrometry. Dynamic tracings of aortic pressure and diameter were recorded simultaneously at standard locations proximal and distal to the stenosis and at comparable sites in noncoarcted control animals. In the proximal aorta, mean blood pressure and pulse pressure were increased (p less than 0.05), but wall motion and intimal lesion area were not different from those determined in control monkeys. In the aorta distal to the coarct, mean blood pressure was no different from that in control animals but pulse pressure was diminished; in addition, there was marked reduction of arterial wall motion (p less than 0.001). This was accompanied by a significant reduction of intimal plaque area (p less than 0.05) and acid lipase activity (p less than 0.001). Thus, inhibition of plaque formation in the distal aorta coincided with reduction of pulse pressure and aortic wall motion rather than with blood pressure or hypercholesterolemia. Inhibition of arterial wall motion may account for the sparing effect often encountered in human arteries distal to stenosing atherosclerotic plaques.

Abstract

In order to identify patients who, having had an initial pulmonary embolism, are likely to develop recurrent emboli despite adequate anticoagulation therapy, ten patients (group 1) with documented recurrent pulmonary embolism during anticoagulation therapy were compared with 31 patients (group 2) who showed no evidence of recurrent emboli during the treatment period. Risk factors for thromboembolic disease were similar between the two groups. Noninvasive venous studies of the lower extremities, including Doppler venous ultrasound and phleborheography (PRG), were performed upon all patients after the initial embolic event. Of the ten patients in group 1, seven (70 per cent) had clinical signs of deep vein thrombosis (DVT). Doppler studies were positive for eight of the nine patients studied, and PRG studies were positive for eight of eight patients tested. In contrast, of the 31 patients who responded well to medical therapy, one patient (3 per cent) had clinical signs of DVT, three patients (10 per cent) had positive Doppler studies and one patient (3 per cent) had a positive PRG. Combined Doppler and PRG studies were positive in 100 per cent of the patients in group 1 but in only 6 per cent of the patients in group 2 (p less than 0.001). The results of this study suggest that patients having an initial pulmonary embolism and DVT of sufficient extent detected by noninvasive studies may be at an increased risk for recurrent PE despite anticoagulation therapy. Insertion of a vena cava filter should be considered in these patients prior to the second embolic event.

Abstract

Profundaplasty has been advocated as an outflow procedure for threatened failure of aortobifemoral grafts as well as a primary procedure for severe claudication and limb ischemia. The authors reviewed their experience with 27 patients who underwent profundaplasty between 1978 and 1983; five patients (group 1) were treated for threatened or complete aortofemoral graft thrombosis while 22 patients (group 2) underwent profundaplasty as an isolated procedure to treat limb ischemia. Preoperative angiograms were assessed for the presence of five criteria associated with a favourable result from profundaplasty: stenosis of the orifice of the deep femoral artery greater than 50%; minimal disease of the distal artery; disease-free collaterals; reconstitution of a patent superficial femoral or popliteal artery; good popliteal outflow with at least one vessel patent to the foot. Profundaplasty was successful in 100% of group 1 patients but relieved symptoms or healed lesions in only 14% of those in group 2. In the latter group 64% required major amputation. The number of favourable angiographic criteria was similar in both groups. Isolated profundaplasty for limb salvage is not recommended. Angiographic criteria do not reliably identify the few patients who will benefit from profundaplasty alone. The principal role of the procedure is increasing outflow for an aortic graft.

Abstract

We reviewed 86 consecutive patients undergoing elective carotid endarterectomy to determine whether preoperative clinical and angiographic data could be used to predict the risk of intraoperative cerebral ischemia during carotid occlusion. Electroencephalographic (EEG) monitoring with on-line Berg-Fourier transformation was carried out in all patients. A total of 32 patients (37.2%) underwent intraoperative shunting. Of these, 13 had no EEG changes but underwent shunting because of the surgeon's preference, while 19 patients underwent shunting because of EEG changes consistent with cerebral ischemia. There was one permanent (1.2%) and one transient (1.2%) neurologic deficit. Angiographic findings, clinical histories, and intraoperative EEGs were retrospectively reviewed to determine which risk factors best predicted the occurrence of intraoperative cerebral ischemia. Stroke within six weeks increased the risk of intraoperative cerebral ischemia 20-fold. Intracranial disease and contralateral carotid stenosis increased the risk of ischemia 17-fold and 16-fold, respectively. Statistical summation of all risk factors yielded a probability equation for EEG change that accurately quantitated pre-operative risk. Prospective application of this probability equation may simplify operative decision making if EEG monitoring is not available.

Abstract

Spectral analysis of the electroencephalogram (EEG) was monitored during 105 carotid endarterectomies. Seventy-eight percent of the patients showed no significant change in EEG spectral power as a result of clamping of the internal carotid artery. Two patterns of change were observed in the remaining 22% of patients: partial reduction (significant decrease of power in one or two of three frequency bands) and global reduction (significant decrease of power in all three frequency bands). High frequencies (over 10.5 Hz) changed more frequently with clamping than did low frequencies (less than 6 Hz), but reduction of high frequencies alone was tolerated with no postoperative deficits. The only non-shunted patient demonstrating global EEG reduction for the duration of carotid clamping suffered a transient hemiparesis.

Abstract

The case is presented of a 38-year-old woman who suffered multiple cerebellar infarctions as a result of emboli from a vertebral artery dissection. Surgical therapy led to a satisfactory recovery. This case emphasizes the importance of an aggressive approach to such lesions.

Abstract

Increased collagenase activity has been implicated as a basic abnormality in aortic aneurysm formation. We studied a localized aneurysmal change, poststenotic dilatation, and its relation to collagenase and elastase activity of the aortic wall. Cynomolgus monkeys underwent midthoracic aortic coarctation to produce poststenotic dilatation. Serial angiography showed that poststenotic dilatation was minimal or absent at 10 days, just discernible at 3 months, and prominent at 6 months. At the 3-month time interval, collagenase activity in the region of the poststenotic dilatation increased twofold compared with the same region in aortas from animals without poststenotic dilatation (p less than 0.05). There was no change in aortic elastase activity. These data indicate that collagenolysis and aneurysmal dilatation may be induced by local modifications of pressure and/or flow. Increased collagenase activity associated with abdominal aortic aneurysms may not represent an intrinsic metabolic defect but rather a response to altered hemodynamic conditions.

Abstract

Though the syndrome of carotid artery dissection is well known, "spontaneous" vertebral artery dissection is rarely recognized. We now report clinical and radiologic findings in five patients with presumed vertebral dissection, one pathologically confirmed. Mean age was 35.2 years (range 27-41). Two were men; three women. None had hypertension, vascular disease, or trauma. Headache and neck or occipital pain was prominent in all, often preceding other symptoms. Four of five patients had unilateral partial alteral medullary syndromes, in one accompanied by medial medullary signs. One patient had a cerebellar infarct. Angiography in four patients showed severe irregular stenosis of the distal extracranial vertebral artery (three bilaterally). A fifth patient with irregular stenosis above the vertebral origin had verified extensive dissection in the resected segment. No patient developed late ischemia. Repeat angiography in three showed healing. We conclude that spontaneous vertebral artery dissection, though rare, has recognizable clinical and radiologic features.

Abstract

Fluid velocities were measured by laser Doppler velocimetry under conditions of pulsatile flow in a scale model of the human carotid bifurcation. Flow velocity and wall shear stress at five axial and four circumferential positions were compared with intimal plaque thickness at corresponding locations in carotid bifurcations obtained from cadavers. Velocities and wall shear stresses during diastole were similar to those found previously under steady flow conditions, but these quantities oscillated in both magnitude and direction during the systolic phase. At the inner wall of the internal carotid sinus, in the region of the flow divider, wall shear stress was highest (systole = 41 dynes/cm2, diastole = 10 dynes/cm2, mean = 17 dynes/cm2) and remained unidirectional during systole. Intimal thickening in this location was minimal. At the outer wall of the carotid sinus where intimal plaques were thickest, mean shear stress was low (-0.5 dynes/cm2) but the instantaneous shear stress oscillated between -7 and +4 dynes/cm2. Along the side walls of the sinus, intimal plaque thickness was greater than in the region of the flow divider and circumferential oscillations of shear stress were prominent. With all 20 axial and circumferential measurement locations considered, strong correlations were found between intimal thickness and the reciprocal of maximum shear stress (r = 0.90, p less than 0.0005) or the reciprocal of mean shear stress (r = 0.82, p less than 0.001). An index which takes into account oscillations of wall shear also correlated strongly with intimal thickness (r = 0.82, p less than 0.001). When only the inner wall and outer wall positions were taken into account, correlations of lesion thickness with the inverse of maximum wall shear and mean wall shear were 0.94 (p less than 0.001) and 0.95 (p less than 0.001), respectively, and with the oscillatory shear index, 0.93 (p less than 0.001). These studies confirm earlier findings under steady flow conditions that plaques tend to form in areas of low, rather than high, shear stress, but indicate in addition that marked oscillations in the direction of wall shear may enhance atherogenesis.

Abstract

Purified acid lipase was previously shown to hydrolyze the artificial substrate, alpha-naphthyl palmitate, as well as triglycerides and cholesteryl esters and to form cholesteryl esters. To determine to what extent these activities are associated with acid lipase-containing cells in atherosclerotic plaques, we examined rabbit aortas at different stages of experimental lesion induction and human atherosclerotic arteries. Assays of cholesteryl ester formation, and alpha-naphthyl palmitate and cholesteryl ester hydrolysis were performed on homogenates of lesions and the hydrolysis of the artificial fatty acid ester was used as a histochemical marker to identify acid lipase positive foam cells in sections of the same lesions. The volume of lesions occupied by cells stained for acid lipase correlated strongly with the enzyme activities of the arterial homogenates. These results suggest that acid lipase-containing cells may mediate the accumulation of cholesteryl ester during atherogenesis. Since acid lipase activity marks macrophages, these methods may be useful for relating macrophage distribution and function to lesion progression, regression, and complication.

Abstract

Doppler ultrasound and PRG were compared with the results of venography in 216 limbs with suspected DVT. Equivocal or conflicting noninvasive test results were obtained in 40 limbs and thrombi were demonstrated venographically in 18 of these (45 per cent). In the remaining 176 limbs, the sensitivity of the noninvasive test was 88 per cent and the specificity was 99 per cent. Treatment may be confidently chosen without venographic confirmation when the results of Doppler ultrasound and PRG agree. Venography is indicated in the minority of instances when the two noninvasive test results do not agree or are equivocal.

Abstract

The role of heart rate in the development of coronary atherosclerosis was assessed in adult male cynomolgus monkeys (Macaca fascicularis). Heart rate was lowered in six animals by surgical ablation of the sinoatrial node. A sham procedure, which included all of the surgical steps except for sinoatrial node ablation, was carried out in eight animals. All of the monkeys were fed an atherogenic high cholesterol diet for 6 months, and heart rates were monitored repeatedly by telemetry during 24-hour test periods. Coronary atherosclerosis in animals with postoperative heart rates less than the preoperative mean for all of the animals that underwent surgery was less than half that of animals with heart rates above the mean or of diet-fed control animals not subjected to surgery. Groups did not differ in blood pressure, serum lipids, or body weight. These results suggest that heart rate in itself may contribute to the mechanisms by which behavioral patterns and physical training influence coronary artery disease.

Abstract

The human abdominal aorta is particularly susceptible to the formation of aneurysms with atrophic walls. This aortic segment normally has fewer medial lamellar units than would be expected for a mammalian aorta of comparable diameter as well as far fewer medial vasa vasorum than would be expected for an aortic wall of comparable thickness. To test the hypothesis that ischemia and/or loss of normal lamellar architecture are predisposing factors for aneurysm formation, we used the pig thoracic aorta, which is furnished with 75 medial layers and vasa supplying the outer two thirds. Vasal blood flow was surgically ablated, and crushing injury was used to reduce the number of intact lamellar units. Mural ischemia alone resulted in necrosis of cells in the medial zone furnished by vasa but did not lead to aneurysmal dilatation, and all the fibrous tissue layers persisted during the 2-month observation period. Mechanical injury resulted in aneurysms in both ischemic and nonischemic aortic segments, but only if fewer than 40 intact lamellae remained and the average tension per lamellar unit exceeded three times the normal value of 1316 +/- 202 dynes/cm (4543 +/- 1624 for ischemic and 4087 +/- 871 for nonischemic segments; p less than 0.01 for each). We conclude that a critical reduction in the number of intact lamellar units results in aneurysmal dilatation. Protracted medial ischemia due to intimal plaque formation in the avascular abdominal aorta may eventually reduce the number of intact lamellae and favor the development of aneurysms.

Abstract

We performed percutaneous transluminal angioplasty (PTA) in 97 limbs of 86 patients with end-stage occlusive disease in whom vascular reconstruction was not possible. Most patients required dilation of long-segment occlusions and/or multiple lesions. Angiographic appearance was improved in 87 limbs of 78 patients (90%). Ankle-brachial pressure index increased from 0.40 +/- 0.03 to 0.64 +/- 0.03, and increased more than 0.15 in 63% of the limbs. Major amputation was required in 19 of the 87 limbs (22%) following PTA. The incidence of restenosis was 19% at three months, 42% at six months, and 57% at one year. Repeated PTA successfully maintained vascular patency in ten limbs, and four patients have since had successful distal bypass. Two limbs that initially improved needed amputation four to 19 months after dilatation. Follow-up ranged from one to 45 months; overall limb salvage rate was 76%. Thus PTA can enhance limb salvage in poor-risk patients with end-stage disease.

Abstract

Cyclic stretching of smooth muscle cells in culture resulted in a two- to fivefold increase in protein and collagen synthesis. The same in vitro system was utilized to relate changes in smooth muscle cell morphology to mechanical stress. Smooth muscle cells, grown in culture from rabbit aorta explants, were transferred to purified elastic membranes derived from bovine aorta. The membranes were either subjected to stretching and relaxation 52 times per minute or stretched and held stationary for 8, 48, or 56 hr. Profiles of rough endoplasmic reticulum (RER) were counted and myofilament content estimated from electron micrographs of 100 cells for each experiment. Cells from cyclically stretched preparations were compared with stationary cells derived from the same subculture. Myofilaments were largely replaced by RER in cyclically stretched cells and there was a reciprocal relationship between RER and myofilament content in individual cells. In cells from stationary preparations, myofilament content also diminished with time but RER profiles were few. At 56 hr, RER profiles numbered 16.7 +/- 1.7 in stretched cells compared with 3.6 +/- 1.3 in stationary cells (P less than 0.05). Cyclically stretched cells formed numerous intercellular contacts and showed little evidence of cytoplasmic degradation while stationary cells showed few contacts and contained numerous cytosomes and lamellar bodies. The results suggest that cyclic stretching resulted in the formation of RER or the preservation of myofilaments and that immobility resulted in the disappearance of myofilaments and cytoplasmic degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

The distribution of nonstenosing, asymptomatic intimal plaques in 12 adult human carotid bifurcations obtained at autopsy was compared with the distribution of flow streamline patterns, flow velocity profiles, and shear stresses in corresponding scale models. The postmortem specimens were fixed while distended to restore normal in vivo length, diameter, and configuration. Angiograms were used to measure branch angles and diameters, and transverse histological sections were studied at five standard sampling levels. Intimal thickness was determined at 15 degrees intervals around the circumference of the vessel sections from contour tracings of images projected onto a digitizing plate. In the models, laser-Doppler anemometry was used to determine flow velocity profiles and shear stresses at levels corresponding to the standard specimen sampling sites under conditions of steady flow at Reynolds numbers of 400, 800, and 1200, and flow patterns were visualized by hydrogen bubble and dye-washout techniques. Intimal thickening was greatest and consistently eccentric in the carotid sinus. With the center of the flow divider as the 0 degree index point, mid-sinus sections showed minimum intimal thickness (0.05 +/- 0.02 mm) within 15 degrees of the index point, while maximum thickness (0.9 +/- 0.1 mm) occurred at 161 +/- 16 degrees, i.e., on the outer wall opposite the flow divider. Where the intima was thinnest, along the inner wall, flow streamlines in the model remain axially aligned and unidirectional, with velocity maxima shifted toward the flow divider apex. Wall shear stress along the inner wall ranged from 31 to 600 dynes/cm2 depending on the Reynolds number. Where the intima was thickest, along the outer wall opposite the flow divider apex, the pattern of flow was complex and included a region of separation and reversal of axial flow as well as the development of counter-rotating helical trajectories. Wall shear stress along the outer wall ranged from 0 to -6 dynes/cm2. Intimal thickening at the common carotid and distal internal carotid levels of section was minimal and was distributed uniformly about the circumference. We conclude that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening. Intimal thickening and atherosclerosis develop largely in regions of relatively low wall shear stress, flow separation, and departure from axially aligned, unidirectional flow. Similar quantitative evaluations of other atherosclerosis-prone locations and corresponding flow profile studies in geometrically accurate models may reveal which of these hemodynamic conditions are most consistently associated with the development of intimal disease.

Abstract

We have treated 13 patients with limb-threatening ischemia caused by acute arterial thrombosis with selective arterial infusion of streptokinase. The indications for thrombolytic therapy included medical contraindication to surgery, surgically inaccessible thrombi, arterial thrombosis following percutaneous transluminal angioplasty, and thrombosed distal arterial bypass. Patients were evaluated with arteriography, Doppler segmental arterial pressure studies, and coagulation profile. Objective evidence of complete or partial thrombolysis was demonstrated in 11 of the 13 patients (85%). Treatment after thrombolytic therapy included percutaneous transluminal angioplasty in six patients and distal bypass in two patients. Of five patients who had received no additional treatment, three required amputation. Overall limb salvage was achieved in 10 of the 13 patients. The most serious complications were puncture site bleeding in five patients, acute renal failure in one patient, and retroperitoneal hemorrhage in another patient. Bleeding was more frequent in patients with decreased serum fibrinogen levels. Although lysis of acute arterial thrombi can be achieved, thrombolytic therapy alone will allow limb salvage in only a few patients. Selective thrombolytic therapy with streptokinase must be used with caution and is associated with serious complications.

Abstract

We studied immediate and long-term alterations in human atherosclerotic arteries subjected to balloon dilatation. Pathologic material included vessels obtained at amputation or autopsy that had been previously dilated in vivo and cadaver vessels dilated under physiologic pressure and temperature. All vessels were pressure-perfusion fixed, and morphologic observations were correlated with sequential angiograms obtained in 36 patients. Balloon dilatation resulted in disruption of both the plaque and the artery wall, with separation of the plaque from the tunica media, rupture of the tunica media, and stretching of the tunica adventitia to increase lumen cross-sectional area. The intimal plaque protruded into the lumen, accounting for the angiographic appearance of local flaps and dissection channels. Remodeling occurred by readherence of the intimal flaps with little change in plaque volume. Achievement of a sufficient radius of curvature may be necessary to achieve long-term patency. Restenosis may occur because of insufficient dilatation but may also result from extention of dissection channels into nondilated segments of the artery.

Abstract

In cases of occlusion of the superficial femoral artery exceeding a length of 10 cm, accompanied by involvement of the popliteal artery and poor runoff, percutaneous transluminal angioplasty is unfavorable. However, when such advanced occlusive disease is present in patients for whom vascular surgery is not feasible, this technique can be of value by averting or at least postponing amputation. Percutaneous transluminal angioplasty was used to recanalize long segments (10-36 cm) of occluded or stenotic femoropopliteal arteries in 21 patients. Results were evaluated by means of pre- and postangioplasty arteriograms and measurements of pressure indices. The initial success rate was 76%; the success rate on 5-24 month follow-up was 67%. The long-term benefit can be improved by other measures, such as stopping cigarette smoking, exercise, long-term anticoagulation therapy, and early detection and treatment of restenosis.

Abstract

Erectile impotence is not a simple problem and it is important to recognize that the presence of a possible organic cause does not rule out emotional difficulties or sexual maladjustment. Behavioral therapy and surgery have an important role in treating this symptom. By careful pre-treatment evaluation the most appropriate therapy can be selected. It has been our general rule that when neither clear organic nor psychogenic problems lie at the root of the difficulty, a trial of behavioral therapy is the most appropriate procedure. If no success is achieved after an adequate trial of therapy re-evaluation and recommendation for a prosthetic implant can be made.

Abstract

The referral pattern of impotent men from a urology clinic to a sexual dysfunction clinic was investigated. Only 62% of referred patients made such recommended appointments. Of the patients for whom sex therapy was recommended, only 32% accepted this recommendation. Of those accepting a recommendation for treatment, 57% prematurely terminated treatment against medical advice. The implications of this for referring physicians and alternative treatment approaches are discussed.

Abstract

We performed a prospective randomized clinical study to determine whether use of a thigh tourniquet influences the incidence of deep venous thrombosis. The lower limbs of patients who were scheduled for elective surgery on the fore part of the foot were randomized and assigned to one of three treatment categories: Group I, no tourniquet; Group II, exsanguination by an Esmarch bandage before tourniquet application; and Group III, exsanguination by elevation of the extremity prior to application of a tourniquet. The 117 limbs of seventy-one patients included in this study were evaluated preoperatively and twenty-four and seventy-two hours postoperatively with 125I-labeled fibrinogen, and preoperatively and seventy-two hours postoperatively with Doppler ultrasound studies and phleborheography. The findings in all of the Doppler ultrasound studies and all of the phleborheograms were normal. Two of the 125I-fibrinogen studies were positive, but subsequent contrast venography revealed that these were false-positive findings. We therefore concluded that the use of a thigh tourniquet does not increase the risk of deep venous thrombosis in patients who have had an operation on the fore part of the foot.

Abstract

We studied 218 patients (372 limbs) and 25 normal subjects (50 limbs) with resting ankle index (RAI), treadmill exercise (TE), and postocclusive reactive hyperemia (PORH) to determine whether diagnostic accuracy is improved through the use of stress testing. In addition, we studied 10 patients with stable claudication (20 limbs) to determine the reproducibility of the three measures. RAI was the most reproducible measure, with the smallest variance between testing days (P less than 0.001). RAI differentiated between arteriographically diseased and normal limbs with a sensitivity of 97% and a specificity of 100%, whereas the corresponding values for TE were 97% and 96% and for PORH 89% and 96%. Recovery to baseline index was prolonged in the diseased group compared with normal (p less than 0.001 for both TE and PORH), but this was of limited discriminative value. Receiver-operating characteristic curve analysis documented that RAI was as diagnostically useful as TE and that both were more valuable than PORH (P less than 0.02). However, the routine addition of stress testing increased diagnostic yield by only 1.6% and cost $1100 for each limb correctly diagnosed through the addition of stress testing. RAI is a simple, accurate, and reproducible test. Routine stress testing is not cost effective, adding little diagnostic information to RAI, and it should be reserved for the small subset of symptomatic patients with normal RAI.

Abstract

A case of abdominal aortic aneurysm with Bechçet's disease and a review of two similar cases previously reported are presented. This case and additional review of other reported major vascular complications of Behçet's disease lead us to conclude that the pathogenesis of the abdominal aneurysm is related to involvement of the aortic wall or vasa vasorum by the Behçet's disease process. Surgical treatment of this rare complication by Behçet's disease should include extra-anatomic bypass if the possibility of infection cannot be definitely excluded.

Abstract

Thirty patients with end-stage atherosclerosis, being considered for amputation, were treated by percutaneous transluminal angioplasty (PTA). All had very poor run-off, and none was a candidate for arterial reconstruction. Occluded segments of the iliac, femoral, popliteal, and tibial arteries measuring up to 21 cm were recanalized, resulting in an increased ankle/brachial systolic pressure index despite significant distal occlusive disease. Ischemic symptoms were relieved in 22 patients, and the overall limb salvage rate (2- to 17-month follow-up) was 73%.

Abstract

Forty-two patients suspected of having unilateral upper extremity deep venous thrombosis (DVT) were evaluated with Doppler ultrasonography and phleborheography (PRG). Venography was performed on 23 upper extremities (54%). Doppler ultrasonography and PRG produced similar accuracy (82%) in detecting upper extremity DVT when compared with venography. The accuracy improved to 91% when the results of both tests were considered together. It is concluded that Doppler ultrasonography and PRG, when used together, are useful, rapid, and accurate techniques for diagnosing upper extremity DVT.

Abstract

We studied 133 patients with arteriographic evidence of lower limb arterial disease and 34 normal volunteers to determine the most useful means of expressing ankle pressure. Representative ranges were determined for each of six symptomatic categories. Receiver operating characteristic curve analysis showed that ankle index (ankle to brachial pressure ratio) and brachial-ankle pressure gradient were more valuable than absolute pressure in discriminating between normal and disease extremities. In contrast, absolute ankle pressure was the best predictor of nonviability (limb requiring bypass for salvage or amputation). An absolute pressure cutoff of 6mm Hg correctly identified 86% of viable limbs and 77% of nonviable limbs. Thus, the diagnostic accuracy of the three methods of expressing ankle pressure depends on the context in which they are to be used, and it appears that ankle index and gradient are most appropriate for defining the presence of disease, while absolute pressure correlates best with viability.

Abstract

Thoracic aortic coarctations were produced in cynomolgus monkeys by one of three methods: circumferential banding to produce a symmetric channel with a rigid wall, lateral plication to provide an asymmetric channel with splitting on one side, and lateral plication plus banding to provide a rigid asymmetric channel. The degree of luminal constriction was 58 +/- 12%, with no significant difference among groups. After 3-12 months on an atherogenic diet, the coarctation channels were remarkably free of lesions compared with the aorta immediately proximal to the coarctation (p less than 0.001). Banding resulted in sharp circumferential termination of the lesions just proximal to constriction. Lateral plication resulted in an oblique termination of proximal disease wtih sparing opposite the plication. Lesions distal to coarctations occurred in a pattern related to the configuration of the coarctation channel and tended to form immediately below the plication. Sparing in and immediately beyond the constriction was independent of the rigidity of the aortic wall or of previous disruptive endothelial or medial injury associated with the operative procedure. Endothelium was preserved within the coarctation channel and over all lesions and distal to the constriction. The findings suggest that flow separation and instability tend to favor atherogenesis, whereas increased flow velocity per se may exert a protective effect.

Abstract

Starling's hypothesis of forces governing fluid movement across capillary membranes suggests that any unopposed decrease in intracapillary colloid oncotic pressure (COP) or increase in capillary permeability should result in increased interstitial fluid. Iso-oncotic increase in pulmonary artery wedge (PAW) causes pulmonary dysfunction. Isobaric reduction of COP with normal capillary permeability does not result in pulmonary interstitial edema. Because sepsis is a frequent antecedent of clinical pulmonary dysfunction, the question was asked: does reduction in the COP-PAW gradient in the presence of sepsis result in increased pulmonary dysfunction? Twenty baboons were studied: group 1--control, group 2--4-h constant infusion of E. coli, group 3--plasmapheresis alone, group 4--plasmapheresis followed by sepsis. Ringer's lactate was infused to keep PAW constant. Arterial and mixed venous blood gases were drawn and the intrapulmonary shunt (QS/QT) was calculated. The data were compared using Tukey's HSD test and one way analysis of variance. Plasmapheresis alone resulted in a 68% reduction in COP (15 +/- 2.9 (SD) torr to 4.6 +/- 0.6 in group 3 and 16.5 +/- 4.3 to 5.7 +/- 0.9 in group 4, p less than 0.05). Sepsis resulted in an increase in QS/QT in all septic animals. There was no increased QS/QT in those animals that had sepsis added to plasmapheresis, group 4 (p less than 0.05). These data indicate that sepsis leads to pulmonary dysfunction but that this dysfunction appears to be independent of colloid oncotic forces.

Abstract

The scientific literature on the treatment of penile erectile dysfunction contains numerous contradictory reports on the relative frequency of organic causes of impotence and the treatment results of behavioral sex therapy. One explanation for these contradictory findings is the hypothesis that different investigators are studying different subsamples of the symptomatic population. This study investigated differences in characteristics of men who initially consulted a urologist with a complaint of impotence versus those who self-referred themselves to a sexual dysfunction clinic. Self-referred sexual dysfunction patients were more often white, more often had psychogenic etiologies to their difficulties, were more often of higher socioeconomic class, and had a much better response to psychological interventions. This study suggests that future studies concerning the etiology and treatment of impotence need to specify population characteristics such as referral source and screening criteria. It may be necessary to develop alternative treatment techniques for men who present to nonpsychiatric sources for help with psychogenic impotence.

Abstract

Patients with a presenting complaint of erectile dysfunction were extensively investigated by a research team consisting of a urologist, vascular surgeon, psychiatrist and psychiatric social worker. Patients were assigned to organic and psychogenic groups according to specified criteria. Multiple comparisons of psychogenic and organic impotence cases on scores derived from the Derogatis Sexual Functioning Inventory (DSFI) did not differentiate the two groups. This inventory did, however, manifest numerous relationships with demographic variables. Failure to identify a psychological profile characteristic of psychogenic impotence was attributed to the heterogenity of this diagnostic grouping and selection processes in seeking treatment for such disorders.

Abstract

Ten patients with symptoms of cerebral ischemia were found to have totally occluded internal carotid arteries with significant external carotid artery stenosis or occlusion. Eight patients underwent external carotid endarterectomy, and two patients underwent saphenous vein bypass to the external carotid artery from the subclavian artery. Cerebral blood flow was measured with 133Xe in six patients preoperatively and in five postoperatively. Four of the six patients had diminished mean flow on the affected side, and three had diminished flow in the contralateral side. All patients had abnormalities in regional cerebral blood flow. Postoperatively, all patients had significant improvement in mean blood flow on the side treated with operation (15% to 39%), and four had improvement of blood flow on the contralateral side (12% to 52%). All had improvement in regional cerebral blood flow. Nine of the 10 patients were relieved of their symptoms. One patient, despite improvement in cerebral blood flow, continued to have diminished cerebral flow and symptoms postoperatively. Subsequent extracranial-intracranial bypass relieved his symptoms and his cerebral blood flow returned to normal. Thus external carotid artery revascularization is effective in increasing total and regional cerebral blood flow and in relieving symptoms of internal carotid artery occlusion and external carotid stenosis. Cerebral blood flow measurement with 133Xe is useful in preoperative patient selection and objective assessment of operative results.

Abstract

Previous investigators have examined the luninal surfaces of perfusion fixed rabbit aortas and reported endothelial damage about aortic ostial flow dividers. These changes have been considered to represent in vivo endothelial injury predisposing to atherosclerosis at these sites. Although standard pressure perfusion fixation techniques were used by these investigators, the fixed aortas were usually cut, bent open and pinned to flat surfaces before viewing. Such procedures distort the aortic media and could result in artifactual endothelial disruptions. We therefore studied the effect of post-fixation aortic manipulation on luminal surface morphology about aortic ostia. Rabbit aortas were fixed by perfusion in situ, while intra-aortic pressure was continuously monitored. When the aortas were opened by means of two parallel, lateral, longitudinal cuts, so that bending and pinning was avoided and normal vessel curvature was maintained, no endothelial disruption occurred about aortic ostia. When aortas were opened with one cut, bent open and pinned flat, ostial flow dividers were somewhat stretched and elongated and there was endothelial disruption in the form of spindle cell formation at the center portion of the flow dividers. Endothelial deformation due to bending during pinning probably occurs preferentially at the flow dividers because the media is thickest at this point. The greater deformability at the adjacent media and differences in compliance between media and intima results in stretching, bending and plication of the intima over the projecting flow divider. Studies attempting to relate endothelial changes to differences in shearing stress about ostia must take into account deformations introduced by post-fixation manipulation.

Abstract

Reduction of blood pressure and serum cholesterol levels is associated with reduced risk for the development of arteriosclerotic disease. Experimental studies indicate that reduced cholesterol levels result in arrest or regression of established diet-induced arterial lesions, but the effects of blood pressure reduction on such lesions are not clear. In order to investigate the effects of blood pressure on the regression of established lesions, we induced aortic intimal disease in cynomolgus monkeys by means of an artherogenic diet, produced midthoracic aortic coarctations, and restored the animals to low-cholesterol diets for 6 months. Diet control animals were neither coarctated nor restored to low-cholesterol diets. Animals with severe aortic stenosis and the regression diet had the same degree of abdominal aortic atherosclerosis and mural cholesterol content as diet control animals but esterified cholesterol and collagen content was elevated. Animals with mild coarctation and consuming the regression diet had significantly less abdominal aortic atherosclerosis than the diet control animals or the animals with severe coarctation. Although stenosis prevented the induction of lesions in previous experiments, the present study indicates that it did not reverse or delay progression of previously established lesions. The effect of pressure reduction on atherogenesis, even in the presence of reduced cholesterol levels, may depend on the extent and nature of the underlying lesions.

Abstract

Six patients with rest pain and gangrene or ulceration were treated by percutaneous transluminal angioplasty using the Grüntzig balloon catheter. All had superficial femoral artery occlusion with severe stenosis or occlusion of the popliteal and tibial arteries. Two patients had previous distal bypass procedures which had failed, and none was a candidate for arterial reconstruction. The superficial femoral artery was recanalized in five patients with an increase in the above-knee pressure index from 0.5 +/- 0.1 to 1.0 +/- 0.1 (P less than 0.001) and ankle pressure index from 0.2 +/- 0.1 to 0.5 +/- 0.1 (P less than 0.001). All five patients avoided early amputation and were able to ambulate when discharged. The sixth patient could not be recanalized and required above-knee amputation. Restenosis of the recanalized superficial femoral artery occurred in four patients 2 to 5 months later, and repeat transluminal angioplasty was successful in three patients. Two patients have required below-knee amputation 4 and 5 months after recanalization. Transluminal angioplasty can extend our capability of early limb salvage.

Abstract

Changes in blood flow to the pelvis were monitored by measurement of penile blood pressures before and after 38 aortoiliac vascular reconstructions. An increase in penile pressure was noted in 14 patients (37%), a decrease was seen in eight patients (21%), and no change occurred in 16 patients (46%). These changes could have been predicted by matching arteriograms to the surgical procedure performed. Preoperative impotence was present in 27 patients (17%). In this group a postoperative increase in penile pressure was associated with restoration of erectile capability in eight of 11 patients. Only one of 10 patients with an unchanged penile pressure regained sexual potency. In contrast, none of the eight patients whose penile pressures decreased had recurrence of erectile capability. Six of these patients had end-to-end aortobifemoral grafts, and concurrent external iliac disease prevented retrograde flow to the internal iliac vessels.

Abstract

The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well.

Abstract

Retrospective analysis of forty-two consecutive patients with flail chest injuries admitted to the Trauma Research Unit of the Naval Regional Medical Center, San Deigo from June 1972 to July 1975 compared ventilatory and nonventilatory management. The actual need for ventilatory support in these patients was determined by analyzing their records for evidence of significant pulmonary dysfunction. This allowed division of patients into three groups: "appropriately" ventilated; "inappropriately" ventilated; and nonventilated. Admission PO2 in the "appropriately" ventilated patients was significantly lower than in the other two groups because the former were admitted with respiratory distress and hypoxemia. Significantly more complications occurred in the ventilated groups than in the nonventilated. Treatment-associated complications were more frequent in the ventilated groups. Because of these findings, we belive that mechanical ventilation should be used in the treatment of flail chest injuries only for significant pulmonary dysfunction and not for the purpose of stabilizing the chest wall. If respiratory support is required, it should be discontinued when normal gas exchange has been restored.

Abstract

Quantitative peritoneal lavage was performed in 52 children with blunt abdominal trauma to determine the presence of intraabdominal injuries. A strongly positive lavage was 100% accurate in diagnosing an intraabdominal injury requiring operation. A negative lavage demonstrated absence of a significant intraperitoneal injury with 100% accuracy. A weakly positive lavage was not diagnostic and required additional evaluation including intravenous pyelography echography, and arteriography. Diagnosis and treatment was prompt, and in 20 of 21 cases, operation was performed within 4 hr. Peritoneal lavage was found to be safe and much more accurate than physical examination in diagnosing significant intraabdominal injury.

Abstract

Thirty-one anesthetized dogs were surface cooled at 5 C and rewarmed after a variable period. Respiration was controlled with a volume respirator. When cardiac arrest occurred, circulation was provided with the mechanical ventricular assistance (MVA) device in 23 dogs. Of the animals maintained for four hours below 10 C on the MVA, 83% were successfully resuscitated. None of the dogs maintained for two hours below 10 C without circulation could be resuscitated. Eleven dogs were studied for a long-term survival after chest closure. Only four of them survived longer than three days. Death after rewarming was due to severe pulmonary insufficiency. Results of this study suggest that provision of oxygenation and a pulsatile circulation during hypothermia improve tissue viability of nonhibernators. The model shows potential for in situ preservation of multiple organs in the cadaver.

Abstract

Twenty-seven anesthetized dogs were surface cooled at 4 to 6 degrees C. or 15 to 20 degrees C. Circulation was provided by the mechanical ventricular assist in 23 dogs. After 24 or 48 hours of in situ preservation, the kidneys were transplanted into the necks or iliac fossas of anephric recipients. Renal function was preserved in the cadaver for up to 48 hours at 15 to 20 degrees C. by maintaining a pulsatile circulation. Further cooling to 4 to 6 degrees C. caused progressive deterioration in renal function. The nonperfused kidneys kept in situ at 4 to 6 degrees C. did not produce any urine after transplantation. If the practical problems of total body cooling are solved, in situ preservation of multiple organs in the cadaver would increase the number of available organs for transplantation.

Abstract

Circulation was maintained in profoundly hypothermic dogs for 8 h at temperatures below 10 degrees C. During cooling to 5 degrees C cardiac output and blood pressure decreased and peripheral resistance rose. Thereafter, circulatory dynamics remained relatively stable over the next 6 h with a gradual decline in blood pressure. The proportion of blood flow to the heart and brain increased with cooling and remained elevated throughout the hypothermia period. Despite continued circulation, pulmonary edema developed after 5-7 h and the dogs were nonviable when rewarmed.